Therefore, in this study, we used two-sample Mendelian randomization (MR) to assess the causal relationship between air pollution (including PM2.5, PM2.5–10, PM10, nitrogen dioxide and nitrogen oxides) and primary liver cancer risk and its related biomarkers (Alpha-fetoprotein, Osteopontin, Glypican-3 and Arginase-1). This evidence concerns the gene SPP1 and liver cancer.