Therefore, to further explore whether there is an association between air pollution and the risk of primary liver cancer, we conducted a Mendelian randomization (MR) study using large-scale publicly available genome-wide association studies (GWAS) data with PM2.5, PM2.5–10, PM10, nitrogen dioxide and nitrogen oxides as exposures and primary liver cancer and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3, and Arginase-1) as outcome to assess the causal relationship between air pollution and the risk of primary liver cancer. This evidence concerns the gene SPP1 and liver cancer.