The bidirectional two-sample Mendelian randomization (MR) was performed primarily using the inverse-variance weighted methods, and sensitivity analysis was carried out simultaneously.<h4>Results</h4>Four immunophenotypes were identified to exert a protective effect against NAFLD, including HLA-DR<sup>+</sup> CD4<sup>+</sup> %lymphocytes, SSC-A on CD4<sup>+</sup>, CD24 MFI on IgD<sup>-</sup>CD38<sup>-</sup>, and CD8 MFI on CD28<sup>-</sup>CD8<sup>br</sup>. Here, CD4 is linked to metabolic dysfunction-associated steatotic liver disease.