Taken together, our study clearly shows that deficiency of TNFR2 on mouse MC38 and CT26 colon cancer cells could markedly impair the growth of the tumor, which may be attributable to the inhibition of AKT signaling pathway, and activation of autophagy and mobilization of antitumor Th1 responses due to reduction of sTNFR2. Here, TNFRSF1B is linked to malignant colon neoplasm.