Purpose At this stage, liver cancer has a poor prognosis and short survival, and there is no clear treatment for this purpose. Therefore, we explored potential future clinical molecular therapeutic targets and biomarkers for survival prognosis prediction that are important for the diagnosis and improved prognosis of patients with hepatocellular carcinoma. METHODS We used multiple databases to analyse genes differentially expressed in hepatocellular carcinoma tissue and normal liver tissue, and also analysed the relationship between genes and clinical features, prognosis and immune infiltration. RESULTS TMEM147 expression levels were significantly higher in hepatocellular carcinoma tissues than in normal liver tissues, and TMEM147 expression levels were strongly associated with pathological stage, body weight, BMI, pathological grade, adjacent liver tissue inflammation, AFP, and vascular infiltration. Survival analysis showed that high TMEM147 expression had a poor survival rate. Also, NK CD56 + cells, TFH cells, Th2 cells, B cells, CD8+, CD4+, macrophages, and dendritic cells were significantly increased and cytotoxic cells, DC cells, neutrophils, Tcm cells, Th17 cells, and TReg cells were significantly decreased in hepatocellular carcinoma patients in the TMEM147 high expression group. Conclusion TMEM147 may be a potential molecular therapeutic target and a biomarker for survival prognosis prediction in the future clinical setting of patients with hepatocellular carcinoma.