Students have been locked in a month-long standoff with authorities and have been boycotting classes as they demand Prime Minister Peter O'Neill step aside over corruption allegations.
Witnesses said the clashes broke out in the capital Port Moresby as students prepared to march from the University of PNG to parliament, where O'Neill was due to face a no confidence vote. Anti-corruption campaigner Noel Anjo Kolao, who helped organise the protest, said police had set up road blocks and pointed their guns at students.
"We have two sets of laws in Papua New Guinea, one for the prime minister and one for ordinary citizens."
PNG broadcaster EMTV said on Twitter that four people had been shot, after earlier reporting that eight students were admitted to hospital, three in critical condition.
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Australia's foreign minister confirmed that students had been shot, while Washington said the police had used tear gas against the protesters. But Port Moresby Hospital's chief emergency physician Sam Yockopua denied reports in Australian media that four people had been killed.
The hospital's emergency department told AFP it was not authorised to give details on patients. Police in Port Moresby did not have any immediate comment.
O'Neill has been wanted for questioning by anti-corruption police for two years, but has refused to comply with a warrant for his arrest.
Police are investigating whether he authorised millions of dollars in illegal payments from the government to Paraka Lawyers, one of the Pacific nation's largest law firms.
When the arrest warrant was issued in 2014, O'Neill sacked the PNG police commissioner, fired his attorney-general and suspended numerous other justice department and police officials.
O'Neil has denied the allegations and last month published a lengthy letter responding to the students' concerns suggesting the accusations were politically motivated.