〔Abstract〕 Objective To investigate the immune exhaustion of CD4+T cells and CD8+T cells in peripheral blood of patients with hepatocellular carcinoma(HCC) and its relationship with disease progression. Methods 30 patients with HCC and 20 healthy subjects(HC) were collected. Flow cytometry was used to detect the frequencies CD4+T cells and CD8+T cell expressing surface inhibitory receptors PD-1, TIGIT, TIM-3 and intracellular IL-10. Cell microsphere array(CBA) was used to detect the content of serum cytokine(IL-10). Results The percentages of TIM-3+CD4+T cells, TIGIT+CD4+T cells, PD-1+CD4+T cells, TIM-3+TIGIT+CD8+T cells, IL-10+CD4+T cells, TIM-3+TIGIT+CD4+T cells in peripheral blood of HCC patients was higher than those of healthy control group(P<0.001), the percentages of TIM-3+CD8+T cells, TIGIT+CD8+T cells and PD-1+CD8+T cells in peripheral blood of HCC patients were higher than those in healthy control group(P<0.01). In addition, the proportions of PD-1+TIM-3+TIGIT+CD4+T cells and PD-1+TIM-3+TIGIT+CD8+T cells in HCC patients were respectively higher than those in PD-1+TIM-3-TIGIT-CD4+T cells and PD-1+TIM-3-TIGIT-CD8+T cells(P<0.001), and serum IL-10 levels in HCC patients were higher than that in healthy controls(P<0.05). ROC curve analysis showed that the frequencies of TIM-3+TIGIT+CD8+T cells and TIM-3+TIGIT+CD4+T cells in the diagnosis of HCC was higher than the percentage of mono-molecule positive cells. The neutrophil/lymphocyte ratio(NLR) of the groups with high TIM-3+TIGIT+CD8+T cells and high TIM-3+TIGIT+CD4+T cells ratio were higher than those of the groups with low TIM-3+TIGIT+CD8+T cells and low TIM-3+TIGIT+CD4+T cells ratio group(P<0.05). Conclusion The proportion of TIM-3+TIGIT+CD4+T cells and TIM-3+TIGIT+CD8+T cells in peripheral blood of HCC patients is higher than that of the control group, and PD-1 is highly expressed in all above cells, which is closely related to IL-10 concentration. And high percentages of TIM-3+TIGIT+CD4+T cell and TIM-3+TIGIT+CD8+T cell are associated with HCC progression disease and poor prognosis, indicating that double molecular targeted therapy may have greater clinical significance than single molecule targeted therapy. Therefore, this work may provide a new and more effective therapeutic target for HCC according to the bimolecular targeted therapy, and promote the development of immune checkpoint targeted therapy for HCC patients.