Israel has come under mounting global pressure after its forces opened fire on the Gaza border on Monday, killing 60 protesters who had massed alongside the fence to protest as the USA moved its embassy from Tel Aviv to Jerusalem.
Calling for "dialogue, justice and peace", Francis said violence "has never led to peace".
He added: "I repeat that the use of violence never leads to peace".
"War calls war, violence calls violence".
At least 2,400 other Palestinians were wounded in what was the bloodiest day of the Israeli-Palestinian conflict since the 2014 Gaza war.
Pope Francis asked all parties involved in the conflict and the whole worldwide community to renew their promise so that dialogue, justice and peace takes precedence.
Pope Francis said he's "very concerned" over the tensions in the Holy Land and the Middle East, which have reignited in recent days with the moving of the USA embassy to Israel to Jerusalem.
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In a statement released on Wednesday, the cardinal said that he had spoken to the Catholic parish priest in Gaza, Fr Mario de Silva, "to offer our prayers and support". He said that knowing Catholics in England & Wales and across the world remembered the people of Gaza and were praying for them was a great encouragement. Their fate is central to peace and peace can never be built on neglect'.
The deadly protests coincide with the relocation of the United States embassy from Tel Aviv to Jerusalem and the anniversary of the "Nakba", or Catastrophe, when hundreds of thousands of Palestinians fled or were expelled from their homes at the time of Israel's creation.
He called for the easing of travel restrictions and for medical supplies to be allowed into Gaza.
'These protests take place against the drastically deteriorating humanitarian situation which leaves little hope and continues to undermine a peaceful resolution.
Francis explained that in the early years of the Church, Baptism was also called "illumination", and the newly Baptized were called the "illuminated", following Jesus words that he is "the light of the world; he who follows me will not walk in darkness, but will have the light of life".
'All violence is destructive to peace efforts and our cry is for a peaceful two state solution with Jerusalem as the shared capital.