STING pathway was involved in 5‐Fluorouracil-triggered cancer-cell-initiated anti-tumor immunity.Higher STING expression was associated with better chemotherapy response and survival in human colon cancer.Chemotherapeutic drug 5‐Fluorouracil reduced tumor burden was dependent on cancer-cell-intrinsic cGAS-STING-IFN signaling. IFN sensed by bone-marrow-derived cells and the elevated anti-tumor T cells were critical to suppress tumor growth. Here, IFNA1 is linked to malignant colon neoplasm.