His plea follows the deaths of at least two military personnel who were killed in explosions at a military airport on the edge of the Syrian capital on Saturday night.
A group monitoring the war confirmed the killings and said eleven people were also wounded in the incident.
The Britain-based Syrian Observatory for Human Rights said the blasts that rocked Damascus are believed to have been caused by an Israeli strike.
Syrian pro-government media initially blamed the blasts on Israel.
But state media later quoted an unnamed Syrian military official as saying the explosions were caused by an electrical malfunction in a munition depot nearby.
The leader of the Catholic Church appealed to the international community and "all the actors involved" to use diplomacy, dialogue and negotiations "in respect for international humanitarian law and to safeguard the lives of civilians".
Addressing people in St Peter's Square, Francis said: "The winds of war are still blowing and troubling news reaches us about the risks of a possible humanitarian catastrophe (in Syria's Idlib province)."
Hundreds of thousands of civilians in the Idlib area have nowhere to flee.
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