Salmonella is a gram-negative bacterium that has an ability of tumor-targeting growth and proliferation. Attenuated Salmonella VNP20009 is a virulence genes-knockout bacterial strain based on Salmonella typhimurium, and it has an advantage of good therapeutic effect and low toxicity. One of the mechanisms of anti-tumor effect of VNP20009 is the induction of inflammatory reaction within tumor tissues. We used B16F10 melanoma model to investigate the mechanism of the anti-tumor effect of VNP20009. VNP20009 treatment effectively inhibited tumor growth and promoted the apoptosis and necrosis of tumor cells. VNP20009 increased the accumulation or infiltration of CD8⁺ T cells and CD11b⁺ monocytes within tumor tissue by raising the level of immune response and thus, induce the production of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) to kill tumor cells by breaking the immuno-evasion barrier in the tumor microenvironment.