OBJECTIVESTumor-associated antigens (TAAs) have been shown to be associated with a variety of connective tissue diseases. However, the role of TAAs in primary Sjögren's syndrome (pSS) patients is still unclear. This study aims to explore the correlation between TAA levels and systemic clinical manifestations and disease activity in pSS patients.METHODSData were retrospectively collected from 108 patients with pSS (pSS group) and 100 healthy subjects (HCs group). Comparison of clinical characteristics and serological parameters between the TAA-positive group and the TAA-negative group. The independent risk factors of TAAs positivity were analyzed by univariate and multivariate regression, and the receiver operating characteristic curve was used to analyze the diagnostic performance of TAAs for pSS-associated interstitial lung disease (pSS-ILD).RESULTSCompared with the control group, the positivity rates of CEA, CA125, CA15-3, and CYFRA21-1 were higher, and the levels of serum CA125, CA15-3, and CYFRA21-1were higher in the pSS group. The incidence of ILD, pleural effusion, pericardial effusion, and ESSDAI ≥5 in the TAA-positive group was higher than in the TAA-positive group. Multivariate logistic regression analysis showed that the incidence of ILD was identified as an independent risk factor for TAA positivity. The AUC of CEA, CYFRA21-1, and NSE in the diagnosis of pSS-ILD were 0.690, 0.840, and 0.872, respectively, and the combined diagnosis could reach 0.952.CONCLUSIONCertain TAA-positive rates and serum levels were increased in pSS patients. The TAA-positive group is correlated with the ESSDAI scores. ILD was an independent risk factor for TAA positivity, and CYFRA21-1 and NSE had the best diagnostic value in patients with pSS-ILD.