Numerous studies have demonstrated the important roles of epigenetic modifications in tumorigenesis, progression and prognosis. However, in hepatocellular carcinoma, the potential link between N 7 -methylguanosine (m 7 G) modification and molecular heterogeneity and tumor microenvironment (TME) remains unclear., Method: We performed a comprehensive evaluation of m 7 G modification patterns in 816 hepatocellular carcinoma samples based on 24 m 7 G regulatory factors, identified different m 7 G modification patterns, and made a systematic correlation of these modification patterns with the infiltration characteristics of immunocytes. Then, we built and validated a scoring tool called m 7 G score., Results: In this study, we revealed the presence of three distinct m 7 G modification patterns in liver cancer, with remarkable differences in the immunocyte infiltration characteristics of these three subtypes. The m 7 G scoring system of this study could assess m 7 G modification patterns in individual hepatocellular carcinoma patients, could predict TME infiltration characteristics, genetic variants and patient prognosis. We also found that the m 7 G scoring system may be useful in guiding patients' clinical use of medications., Conclusions: This study revealed that m 7 G methylation modifications exerted a significant role in formation of TME in hepatocellular carcinoma. Assessing the m 7 G modification patterns of single patients would help enhance our perception of TME infiltration characteristics and give significant insights into immunotherapy efficacy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Hu, Liu, Feng, Zhang, Han, Liu and Meng.)