The chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing (CMTM) family refers to an updated gene family involved in diverse pathophysiological processes. However, the effect exerted by CMTM family members (CMTMs) in hepatocellular carcinoma (HCC) is still elusive. Herein, to elucidate the expression, prognostic value, and immune roles of CMTMs in HCC, a comprehensive bioinformatic analysis was carried out. Our findings showed that CKLF, CMTM1, CMTM3-4, and CMTM7-8 displayed higher mRNA expression levels in HCC tissues than in normal tissues, yet CMTM2, CMTM5, and CMTM6 were lower in HCC tissues. The levels of CMTM1, CMTM2, and CMTM4 were related to tumor stage. Survival analysis showed that high levels of CKLF, CMTM1, CMTM4, and CMTM6-7 were associated with shorter overall survival (OS). Conversely, a high level of CMTM5 in HCC patients was associated with improved OS. We also found that CKLF, CMTM1-4, and CMTM6-7 were closely correlated with immune infiltration in the HCC microenvironment. In conclusion, this study indicates that CMTMs exert a crucial effect on HCC microenvironment remodeling. CKLF, CMTM1, CMTM4, and CMTM6-7 are potential targets of precision therapy, and CMTM5 is a tumor-suppressive gene that was associated with improved survival in HCC patients.