"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.
Deal now has 34 backers in the Senate, the number needed to uphold Obama's veto
Rome is ready to 'reactivate' controls as 'a temporary measure to allow Bavaria to reorganise and face the emergency'
EU is set to maintain until March 15 sanctions targeted against almost 200 Russian firms & individuals, as well as Ukrainian separatists
During 4-day visit, rights chief is expected to address allegations of rights violations, sexual abuse by UN peacekeepers
Two government-chartered ships carrying some 4,300 people, most of them refugees from war-torn Syria, docked at Athens' Piraeus port
Army claims to have retaken strategic town on Cameroonian border from notorious militant group
The Israeli minister for Culture Miri Regev has said that the Palestinian women who saved a 12 year old boy from an attack by an Israeli soldier should have been shot.
Reports are emerging of Czech police forcibly removing Syrian refugees from trains to Germany and numbering the refugees on their forearms
Hundreds of refugees have protested outside the main railway station having being left stranded outside Budapest railway station with police blocking entry
If UK government separated issues of immigration and asylum, Labour leader candidate says Britons would respond to humanitarian crisis
Demonstrators rallied in Vienna against ill-treatment of refugees after 71 people were found dead in an abandoned truck last week
The Independent newspaper has revealed that Ultra Orthodox children in kindergarten, with some younger than age 3 are being taught to hate anyone who is not Jewish
The far right party has left the coalition with the party leader Oleg Lyashko criticizing the Ukrainian leadership saying that granting regional powers was a conspiracy.
Media reports say earlier self-proclaimed Donetsk and Luhansk republics were preparing a referendum on accession to Russia
Nuclear power increase may help RSA solve its problem of electricity shortage, regular power cuts
Herds of cattle and their owners are are now another target in the sectarian violence of the Central African Republic