"I forcefully ask that children, the sick, the elderly and women, and all civilians do not become the victims of the conflict," he said at his weekly address to thousands of people in St. Peter's square.
"May humanitarian rights be respected, above all in Gaza, where it is urgent and necessary to guarantee humanitarian corridors to help the entire population," he said. Francis spoke as Israel was readying its troops for a ground assault in retaliation for unprecedented attacks it suffered when fighters rampaged through its towns shooting men, women and children and seizing hostages.
"So many have already died. Please, no more spilling of innocent blood either in the Holy Land or in Ukraine or anywhere else. Enough! Wars are always a defeat, always" he said.
Some 1,300 people were killed in the unexpected onslaught, while Gaza authorities said more than 2,300 people had died, a quarter of them children, and nearly 10,000 wounded as Israel responds with intense bombardment to the aggression.
Francis called for prayers to counter "the diabolical force of hate, terrorism and war" and urged believers around the world to join Catholics in the Holy Land in a day of fasting and prayer for peace on Tuesday.
On Friday the Vatican offered to mediate in the conflict.
Cardinal Pietro Parolin, the Vatican's Secretary of State, said the attack by Hamas on Israeli citizens was "inhuman."
Referring to the Israeli response and the widely expected ground assault, Parolin said "it is the right of those who are attacked to defend themselves, but even legitimate defence must respect the parameter of proportionality."