ABSTRACT: We analyzed 801 primary HCC developed in 720 patients. Samples were collected from 1992 to 2016 in three French tertiary liver centers in patients treated by liver resection, liver transplantation (surgical samples) and in patients treated by radiofrequency ablation and with advanced HCC treated by non-curative therapies (tumor biopsies). All samples obtained from surgical samples or tumor biopsy were immediately frozen in liquid nitrogen and stored at -80°C prior extraction. We assessed mRNA expression by quantitative RT-PCR in a subset of 757 liver tumor samples. 517 to 782 HCC, according to the gene considered, were sequenced for 30 driver genes (TERT, TP53, CTNNB1, AXIN1, PIK3CA, ARID1A, ARID2, RPS6KA3, NFE2L2, CDKN2A, IL6ST, BRAF, STAT3, HNF1A, JAK1, KRAS, GNAS, KEAP1, IRF2, HRAS, NRAS, TSC2, APOB, TSC1, ALB, CDKN1A, MAP1B, SETD2, ATM and MLL2).