Abstract: Objective To explore the effects of tumor mutational burden（TMB） and the genetic aberrations in key signal pathway genes on survival prognosis of hepatocellular carcinoma（HCC）. Methods The whole exon sequencing data of 376  and 243 HCC patients were downloaded from the TCGA and schulze2015 cohort of cBioPortal，respectively. Whole genome sequencing data of 394 patients of JP and 250 patients of FR were obtained from ICGC. The relationship of TMB and genetic aberrations in key signal pathway genes and prognosis in HCC patients was analyzed by survival analysis. Results In the TCGA，JP，schulze2015 and FR cohorts，TMB after logarithmic transformation was correlated with age（P<0.001）.In schulze2015，TMB after logarithmic transformation was correlated with tumor size（r=0.204，P=0.002）. In TCGA，OS and DFS of HCC patients in the high TMB group were significantly lower than those in the low TMB group（P<0.001，P＝0.088）. The risk of death in HCC patients in the high TMB group was 2.156 times higher than that in the low TMB group（P<0.001）.There was no association between TMB and OS and DFS in both JP and FR. In TCGA，JP，and FR cohorts，it was found that the median DFS，OS of HCC patients with genetic aberrations in cell cycle control pathway genes were lower than those without variation（P<0.05），while the risk of recurrence and death of HCC patients with genetic aberrations in cell cycle control pathway genes were higher than those without variation（P<0.05）. Conclusion High TMB  and genetic aberrations in cell cycle control pathway genes were associated with poor prognosis in HCC patients.

Key words: Hepatocellular carcinoma, Tumor mutational burden, Prognosis, Cell cycle control pathway