Our study demonstrates that heat-killed Bifidobacterium and Lactobacillus strains induce the intrinsic apoptosis of human colorectal carcinoma RKO cells in vitro and that heat-killed L. casei MG4584 and L. reuteri MG5346 have strong anti-tumor effects in an RKO cell-derived xenograft model through the activation of caspase-9, -3, and -7 and PARP. This evidence concerns the gene CASP9 and neoplasm.