The present study aimed to investigate the expression and effect of cytochrome c (Cytc) in patients with primary Sjogren's syndrome (pSS). In total, 35 newly diagnosed pSS patients and 35 healthy subjects were enrolled in the present study. The mRNA expression levels of Cytc were detected using reverse transcription‑polymerase chain reaction and RT‑quantitative PCR. The expression of the Cytc protein in labial salivary glands was detected by immunohistochemistry and was associated with the integral optical density (IOD) of clinical and laboratory variables. In addition, the content of Cytc in the cytoplasm and mitochondria were examined. The mRNA and protein expression levels of Cytc, and the content of Cytc in the cytoplasm of the pSS patients was increased significantly compared with the healthy controls (P<0.05). The content of Cytc in the mitochondria was significantly decreased compared with the healthy controls (P<0.05). The IOD of Cytc protein levels was positively correlated with immunoglobin G (r=0.8142, P<0.05) and erythrocyte sedimentation rate (r=0.7512, P<0.05). Cytc was upregulated in the pSS patients, indicating the potential role of Cytc in the pathogenesis and development of pSS. Further studies may facilitate the development of targeting this molecular pathway for the treatment of pSS.