"Police opened fire after protesters hurled home-made bombs and pelted stones at them," a witness told AFP in Tuticorin, where at least 12 people were killed on Tuesday in police firing.
The protesters have been demanding the closure of a copper plant owned by British mining giant Vedanta Resources which they say is causing environmental damage.
Pramod Madhav, a correspondent for Indian, English-language news channel Mirrow Now, said the situation is volatile.
In a message posted on Twitter, he said there are unconfirmed reports that at least one person is dead and three more have been injured in the fresh violence.
On Tuesday, protesters rampaged for hours in the southern state of Tamil Nadu calling for the closure of the plant.
"We have confirmation of 12 people being killed in police firing. We fear the toll may rise," the officer told AFP from the state capital Chennai.
An unknown number of protesters were injured in the skirmishes, he said.
Protesters carry the injured. Source: Reuters
Some 20 police were also injured in the clashes in Tuticorin, about 600 kilometres (375 miles) south of Chennai.
The shootings caused immediate outrage. Rahul Gandhi, leader of the opposition Congress party, said it was "state sponsored terrorism".
Protesters stormed the office of the top local administrator and set it ablaze after they were denied permission to hold a rally at the smelting plant.
The police officer said efforts to disperse the 5,000 strong rock-throwing group through a baton charge and tear gas volleys failed. Police then fired live ammunition, he added.
Another officer said more than 110 vehicles were burnt during the disturbances that lasted nearly four hours.
Tamil Nadu chief minister Edappadi K. Palaniswami ordered an inquiry into the shootings but defended the police.
"The police had to take action under unavoidable circumstances to protect public life and property as the protesters resorted to repeated violence... police had to control the violence," he said in a statement.
The families of each victim would be offered one million rupees ($14,700) compensation, he added.
Actor Siddarath condemned the police shootings, calling it a "dark day in our history" and said he would be praying for "the murdered innocents".
Opposition leader and working president of the Dravida Munnetra Kazhagam political party, M K Stalin, called for accountability from the police.
"Where does the final accountability lie for the brutal murder of at least 11 Tamils?" he said in a message posted on Twitter.
Controversial factory
Residents have been protesting for months against the plant run by a Vedanta subsidiary, Sterlite Copper.
Environmentalists and locals allege the plant is contaminating water resources, a charge denied by the company.
The protests have intensified after Vedanta, owned by an Indian billionaire but with its head office in London, sought to expand the plant.
The plant -- which is currently non-operational -- has a 400,000-tonne annual capacity.
It was shut briefly after an alleged gas leak in March 2013 that left hundreds with breathing difficulties, nausea and throat infections.
India's federal green court allowed it to be reopened.
The company maintains that it adheres to environmental standards and accused vested interests of spreading "false propaganda" about its operations.
Tamil Nadu is one of India's most industrialised and prosperous states and similar protests over environmental concerns have turned deadly.
Tuticorin witnessed violent demonstrations in 2012 over a nuclear power plant in neighbouring Kudankulam district that left one person dead.
Thousands of protesters blocked roads to prevent supplies reaching the Russian-built plant, concerned about safety standards. One of the plant units is operational.
In 2016, the Indian arm of global consumer goods giant Unilever settled a 15-year-old suit with hundreds of its former employees over mercury contamination at a thermometer factory in Kodaikanal.
The factory was shut in 2001 after it was found to have disposed mercury waste with following proper protocol.
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