"Can we get out of this spiral of sorrow and death? Can we learn once again to walk and live in the ways of peace?" he asked.
"Yes, it is possible for everyone!" he declared. He called on every person, including those who govern nations, to say "yes" to peace.
The Pope placed the Crucifixion of Jesus Christ at the center of his homily.
"My Christian faith urges me to look to the Cross. How I wish that all men and women of good will would look to the Cross if only for a moment!"
"In the silence of the Cross, the uproar of weapons ceases and the language of reconciliation, forgiveness, dialogue and peace is spoken," he explained.
The Pope reflected on the goodness of creation as taught in Genesis, where humanity is "one family, in which relationships are marked by a true fraternity."
In the beginning, mankind's relationship with God "mirrors every human relationship and brings harmony to the whole of creation," explained Pope Francis.
Although the world is now marked by sin, this original goodness should inspire us, the Pope urged.
"This evening, in reflection, fasting and prayer, each of us deep down should ask ourselves: Is this really the world that I desire?"
Each person must realize that "to be human means to care for one another," he continued, calling this a way to peace.
"Dear brothers and sisters: forgiveness, dialogue, reconciliation. These are the words of peace in beloved Syria, in the Middle East, in all the world," the Pope said.
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The Pope's vigil remarks followed a recitation of the rosary with meditations from the writing of St. Therese of Lisieux.
At the start of the vigil, an image of Mary known as "Salus Populi Romani," the "Protectress of the Roman People," was placed near the altar to serve as an inspiration for prayer.
After his homily, Pope Francis joined tens of thousands of people in silent adoration before the Eucharist. He noticeably clutched his own pectoral cross.
After the Liturgy of the Hours prayers, the evening concluded with Benediction.
Thousands of other prayer vigils are being held around the world in response to the Pope's call to prayer.
Greg Burke, senior communications adviser to the Holy See's Secretariat of State, said Pope Francis has engaged in a "major peace initiative" in response to the Syria crisis.