In summary, we established a non-invasive ​​SIC for HBV-HCC patients after TACE treatment, which can predict the clinical response of patients and indicate the immune exhaustion phenotypes (CD4+TIGIT+PD1+T cells, CD8+TIGIT+TIM3+T cells) and plasma proteins (Gal9, IL8, TNFRSF4) were closely correlated with overall survival after TACE treatment. Here, CD4 is linked to hepatocellular carcinoma.