The minister, Du Qinglin, was speaking to parliamentarians after China reported two new human cases of the potentially lethal H5N1 strain.
Officials are worried that wild birds will infect farm poultry as they return from their winter migration.
"We must remain on a high-level alert in all areas ... and step up prevention and control work," the minister said.
"The possibility of a massive bird flu outbreak cannot be ruled out," Mr Du said in a briefing to MPs.
In 2005, China was hit by more than 30 outbreaks of bird flu.
In their efforts to bring the epidemic under control, authorities have slaughtered more than 23 million birds and embarked on a massive vaccination drive.
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