Father Santoro stopped in the ancient town of Antioch during a pilgrimage to Turkey had undertaken in 1993. He referred to Turkey as "the great land where God chose to speak to mankind in a special way". On this trip, he met with the Orthodox Abouna, who seeing his passion for Turkish Christians, gifted him a small piece of iron that was broken off from (what the Greek Orthodox church of Antioch holds as tradition) from one of the nails used in the Crucifixion. Moved by such a gracious gift, he brought it home to Rome on his return and began asking his superiors for him to be allowed to return to Turkey.
This request was eventually granted, and he returned to Turkey as a "fidei donum" missionary. Early in his stay, he struggled with learning the Turkish language which he felt was critical in missionary work. He would tell Mariagrazia Zambon, a friend in Turkey:
"Turkish is a very difficult language. I am last in class and I don’t know how things will turn out, but being last has its advantages. It helps you know what real, day-to-day humility means. In preparing my homilies, I realized that my limited command of the language forces me to focus on the essential. Being something new for me I can better understand the newness of the Gospel. Since my worshipers from different backgrounds – though most of whom are former Muslims – I am forced to go to the heart of the message and show its unsuspected riches.”
He would eventually leave the town of Urfa and serve at Saint Mary's parish church in Trabzon. Though the town officially only had 15 Roman Catholics, it had a sizable Orthodox community and was a hub in the Eastern European sex trade. On his arrival, he wrote in his newsletter Finestra per il Medio Oriente that his goal was to:
“Open a window that would allow Western and Eastern Churches to exchange gifts, rediscover the sap that flows from the Jewish roots into the Christian tree, encourage a genuine and respectful dialogue between Christianity and Islam"
He again wrote to his friend regarding an incident regarding his concern and passion for helping the women caught up in the sex and prostitution trade in the city:
"We walked by a club where we knew there were young women, mostly Armenian Christian. They invited us in for tea. Sister Maria was with me and she was wearing a cross around her neck. I told the women she was a nun. We chatted about their children, the monasteries in their homeland, how hard it was to live back home. One of them told us that she was a pediatrician by profession. A few days later, we were walking along the neighborhood's main street, praying. A woman who took her clients in a back alley saw Sister Maria’s cross around her neck and came towards us waving. She kissed the nun’s cross and hands, made the sign of the cross and hugged her, asking her if she needed anything. At that point, the pimp followed her, annoyed, but I told him the woman was Christian like us. Local clubs are full of women, often very young. What can be done? Every day, I ask the Lord to open a door for us, to lead some of the women away from that life, to touch the heart of some of the pimps, to send someone who can help us”
Two months before his martyrdom, he spoke again to Mariagrazia Zambon in Iskenderun saying:
“Often I ask myself: What am I doing here? And the words of John the Baptist would come to mind. ‘And the Word became flesh and made his dwelling among us’. I live among these people so that Jesus can live among them through me. In the Middle East, Satan continues to destroy, remembering and loyal to the past. As it was at the time of Jesus, silence, humility, the simple life, acts of faith, miracles of charity, clear and defenseless witness, and the conscious offering of one’s life can rehabilitate the Middle East. I am convinced that in the end there are no two ways, only one way that leads to light through darkness, to life through the bitterness of death. Only by offering one’s flesh is salvation possible. The evil that stalks the world must be borne and pain must be shared till the end in one’s own flesh as Jesus did.”
After speaking his, Mariagrazia said that looked at his watch, stood up, and left the room quickly so that he wouldn't miss his flight back to Trabzon.
On February 5th, 2006, Father Santoro was kneeling in prayer at the Santa Maria church when a man walked up, shouted "Allahu Akbar" and shot him once in the back of his head with a 9mm pistol. Oguzhan Akdin, a 16 year old student was arrested two days later, carrying the weapon used in the murder. He stated to the police that the murder was due to the Jyllands-Posten Muhammad cartoons controversy, when the Danish newspaper had published cartoons of Muhammad that had sparked massive Islamic protests.
Oguzhan was sentenced to 18 years for the premediated murder in a juvenile court on October 10th, 2006. The Bishop Luigi Padovese stated that both Oguzhan and his mother showed no remorse during the trial. In press statements, Oguzhan's mother compared him to Mehmet Ali Agca who attempted to assassinate Saint Pope John Paul II in 1981 and that the crime he had committed:
"was committed in the name of Allah and was a gift to the state and the nation"
Oguzhan was released from jail in 2016 following the attempted coup d'etat attempt in Turkey having served less than 10 years for the murder.
Pope Benedict XVI spoke of his martyrdom at the Shrine of Meryem Ana Evi on November 29th, 2006 in Ephesus.