Here we constructed S-15 successfully, and demonstrated that S-15 in combination of Akt inhibition promote the expression of CD45RA−CCR7+ and downregulates the expression of PD-1+Tim-3+ in human Tils from the patients with HCC, in addition S-15 in combination Akt inhibition decreases the Tregs in Tils and increases the IFN-γ producing tumor infiltrating CD8+ T cells without affecting their expansion. Here, IFNG is linked to hepatocellular carcinoma.