Thousands of people protested across Egypt after Cairo announced its plan to hand over two uninhabited islands to Saudi Arabia. Regime critics accuse President el-Sissi of trading land for Riyadh's financial support.
Egyptian police fired tear gas at protesters and detained some 50 people after the Friday rallies, security officials said.
The demonstrators in Cairo, Giza and Alexandria called for President Abdel-Fattah el-Sissi to resign, chanting "we don't want you, leave," and "Sissi - Mubarak" in reference to strongman Hosni Mubarak who was toppled in 2011.
"The youth of the revolution are still here," 29-year old engineer Abdelrahman Abdellatif told Reuters news agency at the Cairo protest. "We are experiencing unprecedented fascism and dictatorship."
Protesters gathered outside the Cairo press syndicate also chanted: "The people want the downfall of the regime," which is the signature slogan of the anti-Mubarak revolt.
Money and land
The wave of protests was sparked by a new demarcation deal with Saudi Arabia, which the government announced during King Salman's visit last week. The document puts the strategic islands of Tiran and Sanafir under Saudi control, ending decades of Cairo rule.
Both governments now maintain that the Red Sea islands rightfully belong to Saudi Arabia, which in 1950 asked Egypt to protect them from a possible Israeli attack.
However, many Egyptians accuse el-Sissi of selling territory to the rich kingdom, as Cairo kept the negotiations secret and announced the finished deal while Riyadh was pledging billions in new loans.
"If we give up the lands now, there will be more future concessions for him to stay in power, for a few more months," said Alaa Morsi, one of the protesters in Cairo.
Waiting on lawmakers
Speaking at the Red Sea coast on Friday, the Egyptian president defended his decision and said the talks were secret to avoid public debate which could have harmed Egyptian foreign relations.
Supporters of the military regime also held smaller rallies on Friday.
The Egyptian parliament still needs to back the demarcation deal before it goes into effect, but most of the lawmakers are firmly in the president's camp.
'Savior' under fire
The latest rallies mark the first significant push against el-Sissi's rule since he came to power in the 2013 coup. Once hailed as nation's savior from Muslim Brotherhood extremists, the former general now faces a series of crisis of trust over corruption, poverty and unemployment.
Last month, the president sacked Egypt's top auditor, Hesham Geneina, who publicly stated that state corruption had cost the country billions of dollars.
In addition, relations with Italy have been strained over the case of Giulio Regeni, a graduate student who was found dead in a ditch outside Cairo. Several human rights groups accuse elements inside state security agencies of torturing and killing Regeni, which Egypt denies.