Objective To detect the expression levels of ERdj5 and XBP1 in the salivary glands of patients with primary Sjögren syndrome (pSS), and analyze the correlation of the expression levels of ERdj5 and XBP1 with salivary gland damage and oral symptoms to explore their significance in the pathogenesis of pSS. Methods A total of 60 pSS patients in the departments of rheumatology and immunology of Xi’an Honghui Hospital and Qinghai Provincial People’s Hospital between January 2020 and June 2021were randomly selected as the case group, and 20 healthy participants in Qinghai Provincial People’s Hospital in the same period were randomly selected as the control group. The mRNA and protein expression levels of ERdj5 and XBP1 in salivary gland tissues were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, and their correlation with histopathology, salivary flow rate, dry mouth degree, and clinical test indicators were analyzed. Results The mRNA and protein expression levels of ERdj5 and XBP1 in the case group were higher than those in the control group (P<0.001). The ERdj5 mRNA expression was positively correlated with the XBP1 mRNA expression in the case group (rs=0.936, P<0.001). The expression levels of ERdj5 mRNA and XBP1 mRNA in the case group were positively correlated with the pathological grade of labial gland (rs=0.344, P<0.001; rs=0.401, P<0.001), dry mouth degree (rs=0.683, P<0.001; rs=0.730, P<0.001), anti-Ro/SSA antibody (rs=0.363, P<0.001; rs=0.350, P<0.001), anti-La/SSB antibody (rs=0.506, P<0.001; rs=0.471, P<0.001), and European League Against Rheumatism Sjogren’s Syndrome Disease Activity Index (rs=0.782, P<0.001; rs=0.865, P<0.001), and were negatively correlated with salivary flow rate (rs=–0.445, P<0.001; rs=–0.526, P<0.001). Conclusion The expression levels of ERdj5 and XBP1 in salivary glands are increased in pSS patients, and they are related to disease activity, anti-Ro/SSA and anti-La/SSB autoantibodies, damage degree of salivary gland and oral symptoms of patients.