This study aimed to analyze the expression of lipid raft protein flotillin-1 in hepatocellular carcinoma and its relationship with clinicopathological features and prognosis. The expression of flotillin-1 in hepatocellular carcinoma was analyzed by TIMER, TNMplot and UALCAN, a comprehensive gene expression database. Western-blot and immunohistochemical experiments were used to detect the expression of flotillin-1 in hepatocellular carcinoma and adjacent normal tissues. GEPIA, LinkedOmics and

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... Plotter databases were used to analyze the correlation between flotillin-1 and the clinicopathological features and stage of hepatocellular carcinoma, as well as the clinical prognosis of patients. Finally, the potential signaling pathway was studied by analyzing the protein interaction network. Database analysis found that flotillin-1 was highly expressed in hepatocellular carcinoma. Western-blot and immunohistochemical experiments confirmed that flotillin-1 was abnormally highly expressed in hepatocellular carcinoma tissues. The expression of flotillin-1 was significantly correlated with the clinical stage, pathological T stage, differentiation degree, TP53 mutation, hepatitis B infection and vascular invasion. Survival analysis showed that patients with high expression of flotillin-1 had poor prognosis. The protein interaction network and signal pathway enrichment analysis found that flotillin-1 may promote the development of hepatocellular carcinoma by regulating RNA-related metabolic processes. In conclusion, flotillin-1 is a potential prognostic indicator and may promote the progression of hepatocellular carcinoma by regulating RNA metabolism.