Soluble immune checkpoint proteins, such as soluble B- and T-lymphocyte attenuator (sBTLA)19, soluble T-cell immunoglobulin and mucin domain-3 (sTIM-3)20, soluble herpes virus entry mediator (sHVEM)21, soluble programmed cell death-1 (sPD-1)22–24, soluble cytotoxic T-lymphocyte associated antigen 4 (sCTLA-4)25, and soluble programmed cell death-ligand 1 (sPD-L1)24,26,27, are linked to the development and prognosis of HCC, and are potential biomarkers and therapeutic targets. The gene discussed is PDCD1; the disease is hepatocellular carcinoma.