The solute carrier (SLC) superfamily genes encode more than 300 members that are responsible for the transmembrane transportation of many essential endogenous and exogenous compounds ranging from nutrients to drugs.SLCs are highly expressed in metabolic organs such as the liver,regulating the homeostasis of metabolites and the disposition of drugs.In contrast to their well-studied roles in physiological and pharmacological processes,little is known about the relationship between SLCs and cancer progression.Here,we aimed to explore the potential role of SLCs in progression and prognosis of hepatocellular carcinoma (HCC),one of the most commonly diag-nosed cancers and leading causes of death worldwide.By performing bioinformatics analyses of HCC dataset from The Cancer Genome Atlas database,we identified three novel signature SLCs(SLC51B,SLC22A15,and SLC2A1) that are indicative of poor prognosis.Further functional analyses suggested the potential regulation of the three prognostic SLCs on cell proliferation and metastasis.Subsequent knockdown experiments performed in HCC cell lines showed that all three prognostic SLCs positively regulated the proliferation of HCC cells,among which SLC22A 15 and SLC2A 1 were required for migration and invasion of the cells,demonstrating remarkable consistency with the roles identified by bioinformatics methods in HCC.Therefore,our study provides a novel prognos-tic biomarker for HCC and reveals the significant roles of SLCs in HCC progression,which might have been undervalued in the past.