Israeli gunfire killed a 20-year-old man and wounded another 51 people as thousands rallied across the West Bank and Gaza to mark Land Day, medical sources said.
Demonstrations also took place in annexed east Jerusalem and across Israel, as well as in Jordan, southern Lebanon and Syria on Friday to mark the annual event that commemorates the deaths of six Israeli Arabs at the hands of Israeli forces during protests against land confiscation in 1976.
Palestinian medical officials said a total of 318 people were injured in clashes with the Israeli army and police, of whom 51 were wounded by Israeli fire.
And one man was seriously hurt after being hit in the head by a tear gas canister.
In Gaza, Mahmud Zakut, 20, was killed in Beit Hanun near the border fence with Israel, emergency services spokesman Adham Abu Selmiya said in a statement sent to AFP.
Witnesses said he was among a group of dozens of young men who went to the northern border in spite of attempts by Hamas police to stop them.
Abu Selmiya said a total of 37 people had been wounded by gunfire throughout the afternoon, most of them in the Beit Hanun area, although at least six were shot and wounded near the border on the outskirts of Khan Yunis.
In the West Bank, a Red Crescent spokesman said 13 people were wounded by rubber bullets, while in east Jerusalem, a senior official of the Fatah movement of Palestinian president Mahmud Abbas was hit in the mouth by a rubber bullet.
The Israeli army had no immediate comment on the Gaza shootings, saying it was only aware of two people injured by live fire, one near the Erez crossing and another near Khan Yunis.
The United States urged restraint by both its ally Israel and the Palestinians.
"We certainly don't want to see any violence by either side," State Department spokesman Mark Toner told reporters.
Rights group Amnesty International said the news that Israeli forces used live ammunition against demonstrators was "extremely worrying."
It also expressed concern at reports that Palestinian security forces tried to prevent demonstrations in the West Bank and Hamas security forces in Gaza beat protesters.
At Qalandia checkpoint north of Jerusalem, Palestinian youths hurled rocks and set tyres alight, and troops retaliated with a barrage of tear gas, rubber bullets and stun grenades, an AFP correspondent and the military said.
In east Jerusalem, around 400 demonstrators waving huge Palestinian flags rallied outside the Old City near Damascus Gate, with another hundred or so outside Lion's Gate, prompting scuffles in both places, AFP correspondents said.
Police were seen beating several demonstrators, and in one case, an officer in full riot gear snatched a Palestinian flag, threw it on the ground and stamped on it.
Jerusalem police said they had arrested 34 people.
In Bethlehem, a man was seriously injured after being hit in the head by a tear gas canister as troops tried to break up a rally of several hundred people by the main checkpoint, medics and an AFP correspondent said.
In the northern West Bank, around 1,000 people rallied at Kafr Qaddum while another 500 people gathered in Iraq Burin, with scores of people suffering from tear gas inhalation.
In Gaza, 37 people were injured by live gunfire after thousands marched from Jabaliya to Beit Hanun, medics said.
But the army said it was aware of hitting only two people, one of whom was a man who "lit a tyre and rolled it at the soldiers" near the Erez crossing, hitting him in the legs.
And military sources confirmed shooting a man in the leg near Khan Yunis after he set something alight close to the border fence.
In Jordan, more than 15,000 people, joined "a peaceful sit-in" at Kafrein, some 10 kilometres (six miles) from the Allenby crossing, security officials said.
There were also demonstrations in northern Israel and in the southern Negev desert as well as in Syria and southern Lebanon.
Friday's demonstrations were a far cry from the bloody confrontations of May 2011 when troops opened fire on protesters along the Lebanon border and on the Syrian Golan Heights, killing 11 and wounding hundreds.
Meanwhile Israel's UN ambassador said his government has made no decision yet on whether it will attend a proposed international conference on a nuclear weapons free Middle East.
But the envoy, Ron Prosor, insisted there could be no accord on a weapons free zone until there is a "comprehensive peace" in the region.
Israel is widely believed to have a nuclear arsenal but has a policy of neither confirming nor discussing the country's atomic capabilities.