Huge sources of lithium deposits that can be used for electric cars are found in the country's western region which an Anglo-Australian company is waiting for the government's approval to mining.
Thousands of demonstrators blocked major roads across Serbia as anger swelled over a government-backed plan to allow mining giant Rio Tinto to extract lithium from the Balkan nation.
In the capital Belgrade, protesters swarmed a major highway and bridge linking the city to outlying suburbs as the crowd chanted anti-government slogans while some held signs criticising the mining project.
Smaller protests were held in other Serbian cities, with small scuffles between demonstrators and counter-protesters in Belgrade and the northern city of Novi Sad, according to local media reports.
"They allowed foreign companies to do whatever they want on our land. They put us on a platter for everyone who can just come and take whatever they want," Vladislava Cvoric, a 56-year old economist said during the protest.
Serbian tennis star Novak Djokovic shared a photograph of the protest on Instagram and commented that "clean air, water and food are keys to health".
"Without that, every word about 'health' is obsolete", Djokovic added.
The protests followed similar demonstrations last week during which masked men attacked one gathering in western Serbia's Sabac — sparking outrage on social media and accusations the government was using hooligans to suppress the movement.
$2.4 billion investment
Substantial deposits of lithium — a key component for electric car batteries — are found around the western town of Loznica, where the Anglo-Australian company is buying up land but is still awaiting the final green light from the state to begin mining.
Rio Tinto discovered lithium reserves in the Loznica region in 2006.
The company intends to invest $2.4 billion (2.12 billion euros) in the project, according to Vesna Prodanovic, director of Rio Sava, Rio Tinto's sister company in Serbia.
Critics have accused President Aleksandar Vucic's government of setting the stage for illegal land appropriations and ignoring environmental concerns.
The demonstrations come months ahead of likely national elections next year, with critics of the protests accusing organisers of stirring controversy to undermine Vucic before the polls.