Background: The expression and mutation of multiple genes are involved in the complicated mechanism regarding the occurrence and development of hepatocellular carcinoma (HCC). The clinical pathological stage of HCC is closely linked to clinical prognosis of liver cancer. This study aims at analyzing the gene expression and mutation pro le of different clinical pathological stages of HCC (stage I, II, III-IV), based on 367 HCC cases included in TCGA cohort. Results: We identi ed a series of targeting genes with copy number variation (CNV), which is statistically associated with gene expression. For instance, compared withthe normal group, CCNE2 gene is highly expressed in the tumor group and speci cstage I group, which are associated withthree CNV types of single deletion, single gain, and ampli cation mutations. Protein interaction network construction and followed "Molecular Complex Detection" analysis indicated that the high expression of some cell cyclerelated genes in HCC, such as TTK, CDC20, ASPM, is positively correlated with CNV. Non-synonymous mutations mainly existed in some genes, such as TTN, TP53, CTNNB1, MUC16, andALB, however, we did not observe the association between thegene mutation frequency and the clinical pathological grade distribution. The rs121913396 and rs121913400 polymorphisms withintheCTNNB1 gene were associated with the high expression of CTNNB1 protein, but not linked to the clinical prognosis of HCC. We performed the random forest and decision tree approachesfor the modeling analysis and identi ed a group of genes related to different HCC pathological grades, such as the lowly expressed VIPR1, FAM99A, and GNA14 genes, or highly expressed CEP55, SEMA3F, and PRR11. Moreover, we conducted a principal component analysis (PCA) to obtain several genes associated with different pathological grades, including SLC27A5, ADAM17, SNRPA, SNRPD2, and ALDH2. Finally, we con rmed the highly expressed GAS2L3, SNRPA, SNRPD2 genes in the HCC tissues, for the rst time, through a Chinese HLivH060PG02 cohort analysis. Conclusions: The identi cation of the targeting genes, including GAS2L3, SNRPA, SNRPD2, provides insight into the molecular mechanisms associated with different prognosis of HCC.