We show, for the first time in our knowledge, that systemic administration of siRNA against STAT3 complexed to DoCh LNP to B16F10 mouse melanoma model resulted in accumulation of the siRNA in tumor tissue, remarkably downregulated the expression STAT3 and the downstream gene PD-L1, and inhibited tumor growth possibly through partial elimination of immune checkpoint. The gene discussed is STAT3; the disease is melanoma.