"There is no justification for the closure of the Rafah crossing," Hamad al-Raqb, a spokesman for the protesters, said in a speech marking the beginning of a four-day sit-in.
"It is unbecoming of the historic relations between Egyptians and Palestinians," he insisted.
Leading Hamas figures and MPs attended the launch ceremony.
Egyptian authorities have tightened their control over the border with the Hamas-run Gaza Strip since last July's ouster of elected president Mohamed Morsi by the Egyptian army.
In recent weeks, Egypt has repeatedly closed the Rafah crossing, which – due to an ongoing, eight-year Israeli siege – represents Gaza's only window to the outside world.
The Egyptian army has also launched a campaign aimed at destroying the network of tunnels linking Gaza to Egypt's Sinai Peninsula, which in recent years had been used to bring vital commodities into the besieged coastal enclave, home to nearly 2 million Palestinians.
Hamas, an ideological offshoot of the Muslim Brotherhood, the group which propelled Morsi to power in the 2012 elections, has controlled the Gaza Strip, since 2007.
The execution of a commander of Hamas for spying on Israel has drawn swift condemnation from the HRW
Riyadh has announced discussions between Saudi and Venezuelan oil minister over ways to boost oil prices
Fighting breaks out between Rwandan rebels and a local Mai Mai militia
Vienna is considering deploying troops and police to the Balkans to reduce the flow of refugees on the route between Turkey and Austria
The country's PM Trudeau is set to pull out Canada's six F18s from bombing Syria
The legislation giving the government control over Poland's public broadcasters and top court prompted a series of demonstrations and harsh criticisms both at home and across Europe
Thousands have protested in Sarajevo against a ban on wearing the hijab in courts and other legal institutions
Hamas in a short Twitter statement that Mahmoud Eshtewi, a local member of the group’s military wing, was killed after he confessed to spying for Israel.
Buhari under fire for saying Nigerians not welcome abroad for high crime rate
Mosques across Britain open up for visitors as part of Visit My Mosque Day in bid to counter negative portrayal of Islam in mainstream media
Amendments will limit future presidents to two 5-year terms in office and officially recognize language of country’s Berber minority
Strikes kill two members of Mujahideen Shura Council, city of Derna’s de facto ruling body, according to local official
'I appeal to the international community to spare no effort to urgently bring parties back to the negotiating table,' Pope Francis says
Move comes despite November ceasefire deal that temporarily halted fighting between Tebu and Tuareg ethnic groups
The barrier stretches some 200 kilometres across about half the length of the frontier between the two neighbours