We found that 1) loss of DDX3X or inhibiting DDX3X resulted in the aberrant accumulation of endogenous dsRNAs in the cytoplasm of breast cancer cells; 2) the accumulation of dsRNAs activated the dsRNA-sensing pathway via mainly MDA5 and activation of nuclear factor kappa B (NF-κB) pathway followed by IFN-β production and enhanced antigen presentation in the DDX3X-depleted cells; 3) DDX3X-depleted cancer cells demonstrated the inhibited cancer proliferation and suppressed tumor growth in in vivo mouse studies. The gene discussed is NFKB1; the disease is breast cancer.