IVW results showed that 18 types of immune cells, including CD45RA+ CD8br AC (OR = 0.926, 95%CI: 0.869–0.988, p = 0.020), CD39+ CD8br %T cell (OR = 0.928, 95%CI: 0.883–0.975, p = 0.003), PDL-1 on CD14+ CD16− monocyte (OR = 0.940, 95%CI: 0.886–0.997, p = 0.039), and IgD+ CD24+ %B cell (OR = 0.950, 95%CI: 0.904–0.998, p = 0.041), had a protective effect on epilepsy occurrence. This evidence concerns the gene CD274 and epilepsy.