Objectives:The purpose of this study was to examine the proportion of CD161 on CD56+Natural Killer(NK) cells in peripheral blood of primary Sjögren’s syndrome(pSS) and investigate its clinical relevance of pSS. Methods:The proportion of CD56+NK cells and CD161 on CD56+NK cells was detected by flow cytometry in 31 pSS patients and 29 healthy controls (HCs). The correlations between proportion of CD161+CD56+NK cells and clinical features and disease activity of pSS were further analysed. Meanwhile, we drew the receiver operating characteristic(ROC) curve to evaluate the diagnostic value of CD161+CD56+NK cells in pSS. Results: The proportion of CD56+ NK cells and CD161+CD56+NK cells decreased markly in pSS patients compared to HCs. The correlation analysis showed that proportion of CD161+CD56+NK cells negatively correlated with WBC,IgA,IgM,IgG,ESSRPI and ESSDAI,and positively correlated with complement C4.The proportion of CD161+CD56+NK cells in pSS patients with decayed tooth, fatigue, arthralgia, skin involvement, primary biliary cirrhosis(PBC),interstitial lung disease(ILD), anti-SSA/Ro60 positive, anti-SSB positive and high IgG was lower than that in negative patients. Furthermore, compared with innactive patients,the proportion of CD161+CD56+NK cells decreased obviously in active patients. The area under the curve(AUC)was 0.7375(P=0.0016),the results indicated that CD161+CD56+NK cells had certain diagnostic value for pSS. Conclusion: This study suggested that the proportion of CD56+NK cells and CD161+CD56+NK cells decreased significantly in pSS patients,and the proportion of CD161+CD56+NK cells negatively associated with the clinical features and disease activity of pSS patients. The CD161+CD56+NK cells may present as a potential target for therapy and a biomarker of disease activity in pSS .