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We develop a Trojan Horse approach to target TNF-α for cancer therapy. We employed phage/yeast display to select non-neutralizing antibodies that can piggyback on TNF-α and co-internalize into cells. The antibody conjugated with toxins killed cancer cells in a TNF-α-dependent manner. Intratumoral injection of engineered E. coli secreting the immunotoxin greatly inhibited the tumor growth in mice and enhanced the anti-tumor tumor-infiltrating immune cells, including N1 neutrophils, M1 macrophages, and activated CD4⁺ and CD8⁺ lymphocytes.