Israel's military said its troops resorted to live fire, and an air strike, after explosive devices and rocks were thrown at them and to prevent breaches of the border fence from the Islamist Hamas-controlled enclave.
At least 191 Palestinians have been killed since the Gaza protests began on March 30 to demand the right of return to lands that Palestinian families fled or were driven from on Israel's founding in 1948, and the easing of an Israeli-Egyptian economic blockade.
Hamas said Friday's protest also marked the 18th anniversary of the launch of the last Palestinian revolt against Israel.
Israel accuses Hamas, against which it has fought three wars in the last decade, of having deliberately provoked violence in the protests, a charge Hamas denies.
More than two million people are packed into Gaza, whose economic plight is a focus of so-far fruitless US-led efforts to restart Israeli-Palestinian peace talks, stalled since 2014.