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Aberrant activation of the immune system has been reported in asymptomatic hyperuricemia (HUA) patients. However, very few studies have elucidated the role of natural killer (NK) cells in this disease.In this study, we evaluated the relationship between NK cells and HUA in 16 control subjects and 20 patients, who were all on a low-purine diet. We analyzed the number of circulating NK cells, its subsets, interferon-γ+, and CD107+ NK cells, by flow cytometry, before and after 4 and 24 weeks of diet control. We also assessed the potential association of the NK cells with clinical measures.The patients consistently had a lower number of NKG2D+ NK cells before and after low-purine diet, even the serum uric acid (SUA) levels <7 mg/dL after diet control. Moreover, a lower number of NK cells and a higher number of CD107a+ NK cells were observed on recruitment. Low-purine diet was benefit on the improvement of the SUA levels, body mass index (BMI), and the number and functions of NK cells. Furthermore, the number of CD3−CD56+ NK cells and NKG2D+ NK cells negatively correlated with the BMI before and after diet control.The consistent lower number of NKG2D+ NK cells and correlated with BMI before and after low-purine diet may be involved in the occurrence and development of HUA.