Although there has been extensive research on the role of programmed cell death-ligand 1 (PD-L1) in hepatocellular carcinoma (HCC), our understanding of the effects of other inhibitory B7/CD28 family members is still limited despite advancements in prognostic tools, more specific, accurate, and robust biomarkers are required to improve HCC patient prognoses. Here, CD28 is linked to hepatocellular carcinoma.