"Let us together resolve to renew our commitment to the Palestinian people," he said in a message marking the International Day of Solidarity with the Palestinian People that falls on November 29.
As the United Nations marks its 75th anniversary, the question of Palestine remains distressingly unresolved, said the UN chief.
The COVID-19 pandemic has decimated the Palestinian economy and undermined the already fragile humanitarian, economic and political situation in Gaza, further entrenched by crippling restrictions on movement and access.
Meanwhile, prospects for a viable two-State solution are growing more distant.
"A host of factors continue to cause great misery, including: the expansion of illegal settlements, a significant spike in the demolition of Palestinian homes and structures, violence and continued militant activity," Guterres said.
He said Israeli and Palestinian leaders have a responsibility to explore every opening to restore hope and achieve a two-State solution.
"I remain committed to supporting Palestinians and Israelis to resolve the conflict and end the occupation in line with relevant UN resolutions, international law and bilateral agreements in pursuit of the vision of two States - Israel and an independent, democratic, contiguous and sovereign Palestine - living side by side in peace and security, within secure and recognized borders, on the basis of the pre-1967 borders, with Jerusalem as the capital of both States," said the UN chief.
He hoped that recent developments will encourage Palestinian and Israeli leaders to re-engage in meaningful negotiations, with the support of the international community, and will create opportunities for regional cooperation.
"We must also do all we can to ease the suffering of the Palestinian people," Guterres said adding that he is extremely concerned by the financial situation facing UNRWA.
He said the agency plays an essential role as the main provider of direct and often life-saving assistance to many of the 5.7 million Palestine refugees.
"I appeal to all Member States to urgently contribute to enable UNRWA to meet the critical humanitarian and development needs of Palestine refugees during the pandemic," Guterres said.
On this International Day of Solidarity, he also extended his heartfelt condolences on the tragic passing of Dr. Saeb Erakat, Palestine Liberation Organization (PLO) Secretary-General and Chief Negotiator for Palestinians in the Middle East Peace Process.
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