Pope Francis said the recent surge of violence between Israelis and Palestinians is "unacceptable."
He denounced "this hatred and vendetta" and appealed for "calm" during his Sunday blessing.
"Do we truly think that we can build peace by destroying the other?" the Pope asked.
Pope Francis has denounced the violent conflict between Israelis and Palestinians, which has drawn renewed attention this week with a surge of deadly air attacks.
The series of airstrikes mark the most violent clashes between Israel and Hamas since the 2014 Gaza War.
The pontiff called the violence "unacceptable" during his Sunday blessing, the Associated Press reported.
He said the deaths of children in particular signals "they don't want to build the future but want to destroy it."
"I ask myself: this hatred and vendetta, what will it bring?" the Pope said. "Do we truly think that we can build peace by destroying the other?"
"In the name of God, who created all human beings equal in rights, duties, and dignity and are called to live as brothers, I appeal for calm," he said.
The Pope also appealed for peace in a tweet on Sunday, reiterating his particular compassion for young victims.
"Let us pray constantly that the Israelis and Palestinians may find the path of dialogue and forgiveness," he wrote.
Israel and Hamas, the militant group that controls Gaza, have exchanged air attacks over the past week that are said to have killed at least 188 people in Gaza, including 55 children, and eight in Israel.
Most recently, Israeli airstrikes on Sunday alone killed at least 42 people according to the AP, the deadliest single attack in the latest round of violence.
In a televised address reported by the AP, Israeli Prime Minister Benjamin Netanyahu said the attacks are continuing at "full-force" and will "take time," despite international efforts to broker a cease-fire.
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