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Hepatocellular carcinoma (HCC), the most common primary malignant tumour of the liver, is notorious for its high mortality rate.Alpinia officinarum Hance (A. officinarum) is a perennial medicinal herb used for the management of abdominal pain, vomiting, and gastrointestinal tumours, and is widely applied as a dietary intervention by the Li ethnic group in Hainan, China. Kaempferide, a bioactive flavonoid isolated from this herb, exhibits promising antitumor properties; however, its precise mechanism against HCC remains incompletely understood. In this study, we demonstrated that kaempferide could inhibit proliferation and migration of HCC cells, induce G0/G1 phase cell arrest and promote the accumulation of ROS, while suppressing xenograft tumour growth in nude mice. Further investigations revealed that kaempferide targeted BNIP3L and suppressed mitophagy, evidenced by elevated P62 levels and reduced LC3-II levels. In summary, kaempferide exerts anti-HCC effects by inhibiting mitophagy via the downregulation of BNIP3L, suggesting its potential role as a therapeutic candidate for HCC.