Objective To analyze the clinical difference between lymphoma and lymphoma with Sjogren's syndrome or undifferentiated connective tissue disease. Methods The clinical data of 31187 lymphoma patients who were initially treated in West China Hospital, Sichuan University from Jan. 2010 to Dec. 2019 were retrospectively analyzed. The 213 patients who diagnosed Sjogren's syndrome or undifferentiated connective tissue disease before lymphoma were included in group A, and 30974 other cases with lymphoma were included in group B. The differences of age, gender, lymphoma subtype, coagulation index, complement, immunoglobulin, immunophenotype and survival rate between the two groups were compared. Results The onset age of group A was significantly higher than that of group B (P＜0.05). The proportion of women in group A was significantly higher than that in group B (P＜0.05). Group A and B were mainly non Hodgkin's lymphoma, Diffuse large B-cell lymphoma is the most common. In group A, there were mucosa associated blocking cell lymphoma (34.4%) and follicular lymphoma (7.7%). In group B, follicular lymphoma (14.4%), mucosa associated blocking cell lymphoma (9.1%). The levels of PT, APTT and FIB in group A were significantly higher than those in group B (P＜0.05). The levels of complement C3 and IgM before treatment in group A and B were significantly lower than those in group B, and the level of IgG in group A was significantly higher than that in group B (P＜0.05). The decrease proportion of complement C3, the increase proportion of IgG and the decrease proportion of IgM in group A were significantly higher than those in group B (P＜0.05). In group A, the positive expression rate of CD5 was the highest, followed by CD20, CD3, the lowest was CD19. In group B, the positive expression rate of C20 was the highest, followed by CD3 and CD19, and the lowest was CD5. The survival rate of group A were significantly higher than those of group B (P＜0.05). Conclusion For female lymphoma patients with older age, decreased complement C3 level, increased IgG level and decreased IgM level, more attention should be paid in screening of autoimmune diseases and hypercoagulable state. Meanwhile, immunomodulatory therapy should be strengthened to improve the immune disorder and delay the progress of the disease.