Methodology for the in vitro classification and/or prognosis of hepatocellular carcinoma (HCC) from a HCC sample is based on the determination of the expression profile of particular gene combinations. For example, in one embodiment, a method comprises measuring the expression level in an HCC sample of at least 8 genes selected from the group consisting of: RAB1A, REG3A, NRAS, RAMP3, MERTK, PIR, EPHA1, LAMA3, G0S2, HN1, PAK2, AFP, CYP2C9, CDH2, HAMP, SAE1, ADH6, DCN, FLJ10159, ALDH1L1, IGF1, LECT2, SLC38A1, SPARCL1, CTNNA2, GLUL, LEF1, MATN2, MME, PFN2, SPINT2, TBX3, and FGFR2; b) calculating 6 subgroup distances from the expression profile; and c) classifying the HCC tumor in the subgroup for which the subgroup distance is the lowest, wherein the 6 subgroups G1, G2, G3, G4, G5, and G6 are defined by the presence (+) or absence (−) of their clinical and genetic features.