Chants of "leave, leave!" directed at el-Sissi marked the first significant wave of street protests since the former army chief became president in 2014.
Riot police first cracked down on protesters in Cairo's twin city of Giza, where demonstrators had gathered at two prominent mosques after Friday prayers and started marching toward Tahrir Square downtown.
Many carried signs reading, "Land is Honor" and denouncing the surrender of the islands. Others chanted, "The people want the fall of the regime" and "Down with military rule!"
Several photojournalists covering the protests were briefly detained near al-Istiqama mosque in Giza, according to witnesses at the scene who spoke on condition of anonymity because they feared for their own safety.
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All unauthorized demonstrations in Egypt are illegal and security forces have, in the past, used lethal force against peaceful demonstrators.
Egypt's state news agency quoted an unnamed official as saying that the protesters were members of the banned Muslim Brotherhood group and that they chanted "anti-regime slogans."
The official said police responded with tear gas after protesters threw rocks at them.
The protesters there chanted, "They sold our lands to the Saudis." Except for a handful of bearded men and female protesters wearing full-face veils, there was little sign of an organized Islamist presence among the demonstrators.
"If we give up the lands now, there will be more future concessions for him to stay in power, for few more months," said Alaa Morsi, one of the protesters, echoing a widely-held notion that el-Sissi essentially sold Egyptian territory in exchange for much-needed Saudi financial support, to shore up his rule.