Nearly 15,000 people on Saturday participated in the protest against Eldorado Gold’s plans to dig in the Halkidiki peninsula.
"Gold is not bringing us closer, it is killing us," chanted the crowd.
Citizen groups believe the digging will drain and contaminate local water reserves and pollute the air with toxic heavy metals including lead, cadmium, arsenic and mercury.
Local officials in Thessaloniki, however, support the mining project and claim it will create hundreds of jobs in the country, where 26 percent of the population is unemployed.
The protests began in 2011, when Eldorado Gold’s subsidiary Hellenic Gold received government approval to dig in the northern peninsula.
On February 16, dozens of activists threw firebombs onto a Hellenic Gold worksite, which injured one guard and damaged equipment.
Greece has been at the epicenter of the eurozone debt crisis and is experiencing its sixth year of recession, while harsh austerity measures have left about half a million people without jobs.