NPC1L1‐mediated LDL was positively associated with rectal cancer (OR = 4.22, 95% CI: 1.21–14.73, p = 0.02) and hepatocellular carcinoma (OR = 82.99, 95% CI: 1.70–4062.70, p = 0.03). Here, NPC1L1 is linked to hepatocellular carcinoma.