Specifically, the IVW method for genetic prediction revealed that increased circulating levels of C-X3-C motif chemokine ligand 1 (CX3CL1) (OR = 0.92; 95% CI: 0.86–0.99; P = 2.19 × 10-2), interleukin-2 receptor subunit beta (IL-2RB) (OR = 0.90; 95% CI: 0.82–0.99; P = 3.79 × 10-2), leukemia inhibitory factor receptor (LIF-R) (OR = 0.95; 95% CI: 0.91–1.00; P = 4.26 × 10-2), and TNF-related apoptosis-inducing ligand (TRAIL) (OR = 0.96; 95% CI: 0.92–0.99; P = 5.51 × 10-3) were associated with a decreased risk of CRC. Here, CX3CL1 is linked to colorectal carcinoma.