This study demonstrated that (i) the expression of NLRP3 in CRC cells could be induced with resistin treatments, and this upregulation could accordingly decrease the cytotoxicity of 5-FU in HCT-116 and DLD-1 cells, (ii) TLR4 and ERK signaling were involved in the NLRP3 expression and the subsequent resistin-induced decrease in cell death, and (iii) fermented quercetin plays a crucial role in the regulation of NLRP3 expression in resistin-treated CRC cells. The gene discussed is NLRP3; the disease is colorectal carcinoma.