Defying prohibitory orders, the protesters tried to lay siege to the plant and refused to pay heed to repeated appeals by authorities to disperse, insisting they will stay put, 500 metres from the Kudankulam Nuclear Power Project site.
Police said they will take action "as per the prevailing situation."
Over 1,000 anti-nuclear protesters led by People's Movement Against Nuclear Energy convener S P Udayakumar tried to march towards the plant but were prevented from proceeding by Rapid Action Force personnel and police, half a kilometre from the site, police said.
Officials said District Collector R Selvaraj and Sub-Collector Rohini Ramdoss and District Superintendent of Police V Bidari held talks with the protesters to persuade them to disperse but they refused to budge.
The area has come under a tight security blanket with over 2,000 police personnel, including 400 RAF, deployed near the site to prevent any untoward incident.
Prohibitory orders are in place in a seven km radius from the plant in view of the siege call given by PMANE, seen as a last ditch attempt to prevent commissioning of the plant.
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Regulatory authorities had recently given the go-ahead for loading the enriched uranium in the plant, whose commissioning was also given the nod by the the Madras High Court.
The first unit of KNPP, an Indo-Russian joint venture, was scheduled for commissioning in December last, but was bogged down by delay due to protests against the project.