Chinese State media has said that Li Keqiang died 10 minutes past midnight despite all-out efforts to revive him.
Li was once tipped to be the country’s future leader but was overtaken by President Xi Jinping.
A trained economist, Li Keqiang held the second highest-ranked position in China, though in recent years, he was widely isolated amongst China’s top leadership.
He was the only incumbent top official who did not belong to Mr Xi’s loyalists group.
Li, who had stepped down as premier in March this year, suffered a sudden heart attack on Thursday and died on Friday while he was in Shanghai.
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His death is being widely mourned on Chinese social media, with many expressing shock and grief – though comments on many posts appear to have been restricted.
Li was known as one of the smartest political figures of his generation.