AIM: To investigate whether changes in the frequency of peripheral natural killer T (NKT) cells were correlated with liver disease in patients who had metabolic predispositions to nonalcoholic fatty liver disease (NAFLD).METHODS: Peripheral blood samples were obtained from 60 Chinese NAFLD patients and 60 age and gender matched healthy controls. The frequency of peripheral NKT cells was detected by flow cytometry. Clinical and laboratory data were collected for further analysis.RESULTS: NAFLD patients had a lower frequency of peripheral NKT cells than healthy controls (1.21% ± 0.06% vs 1.62% ± 0.07%, P ＜ 0.001). Further analysis revealed that the frequency of peripheral NKT cells was negatively correlated with body mass index, waist circumference and serum levels of alanine aminotransferase. Logistic regression analysis revealed that elevated body mass index [hazard ratio (HR):2.991], aspartate aminotransferase levels (HR: 1.148)and fasting blood sugar (HR: 3.133) increased the risk of NAFLD, whereas an elevated frequency of peripheral NKT cells (HR: 0.107) decreased the risk.CONCLUSION: Changes in the frequency of peripheral NKT cells were correlated with NAFLD and a decreased frequency of peripheral NKT cells was a risk factor for NAFLD.