Background: RNA methylation modifying plays an important role in the occurrence and progression of a range of human cancers including hepatocellular carcinoma (HCC), which is characterized by a mass of genetic and epigenetic alterations. However, the treatment targeting these alterations is limited.Methods: We used comprehensive bioinformatics analysis to analyze the correlation between cancer- associated RNA methylation regulators and HCC malignant features in network datasets. Results: We identified two HCC subgroups (cluster 1 and 2), which had clearly distinct clinicopatholog- ical, biofunctional and prognostic characteristics, by consensus clustering. The cluster 2 subgroup cor- related with malignancy of the primary tumor, higher tumor stage, higher histopathological grade and higher frequency of TP53 mutation, as well as with shorter survival when compared with cluster 1. Gene enrichment indicated that the cluster 2 correlated to the tumor malignancy signaling and biological pro- cesses. Based on these findings, an 11-gene risk signature was built, which not only was an independent prognostic marker but also had an excellent power to predict the tumor features. Conclusions: Our study indicated that RNA methylation regulators are vital for HCC malignant progression and provide an important evidence for RNA methylation, methylation regulators are actionable targets for anticancer drug discovery.