We investigated associations between genetically predicted levels of IL-6 and TNF-α signaling pathways and mortality in people with CRC.<h4>Methods</h4>We conducted a two-sample Mendelian randomization (MR) analysis using cis-acting single nucleotide polymorphisms (SNPs) associated with soluble IL-6 receptor alpha (sIL6-RA) and IL-6 signal transducer gp130 (IL6ST), representing IL-6 signaling, and with TNF-α, and its soluble receptors (sTNF-R1, sTNF-R2). Here, IL6ST is linked to colorectal carcinoma.