To investigate the mechanism by which swertiamarin (swertianin, SWE) regulates the polarization of tumor microenvironment-associated macrophages to M1 phenotype, thereby exerting anti-tumor effects.SWE promoted the formation of M1 cells and increased the proportion of CD86 + cells in both RAW264.7 and primary monocyte-derived macrophages, while activating the STING-NF-κB pathway. When STING or P65 was knocked out, the effects of SWE were antagonized, inhibiting the formation of CD86 + M1 cells. At the animal level, SWE inhibited tumor growth, activated STING-NF-κB, and promoted the formation of CD86 + cells. STING-KO inhibited the effects of SWE.SWE can activate the STING-NF-κB signal to promote macrophage M1 polarization, playing an anti-tumor role.