The combination therapy significantly reshaped the tumor microenvironment (TME) after si-STAT1 transfection.<h4>Conclusion</h4>The combination of H101 and APA exhibited excellent anti-HCC efficacy, which may reshape the TME partially through the IFN-γ/STAT1/PD-L1 axis. The gene discussed is IFNG; the disease is hepatocellular carcinoma.