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Police and fire officials said the toll may rise, as firefighters struggled to enter the building of Omshakti fireworks factory.
Thirty people have died, police and fire officials at the spot said.
"These are times ahead of Deepavali. So activities go on at breakneck speed in the cracker units," Virudhunagar District Superintendent of Police Najmul Hoda said.
A factory official said 300 persons were at work at the unit at the time of the incident.
The fire broke out when fancy cracker items were being made at the factory at Mudalipatti, nine km from Sivakasi, police said, adding all 48 sheds in the premises were gutted.
Fire officials said due to the variety of chemicals used in pyrotechnics crackers, there was thick and suffocating smoke, making the task difficult for fire fighters.
"We are not able to see ahead. The smoke is choking the personnel," an official told PTI from the spot where 10 fire tenders fought the blaze. The smoke could be seen 1.5 km away from the spot.
In October 2009, 32 people, most of them Deepavali shoppers, were killed at a cracker godown fire in Pallipattu in Tiruvallur district.
