To investigate the clinical manifestations and risk factors in patients with systemic lupus erythematosus (SLE) and cancers. From October 2010 to February 2019, 5 566 SLE patients hospitalized in the First Affiliated Hospital of Zhengzhou University were enrolled. A total of 69 cancer patients were identified, and the clinical characteristics and previous treatment were analyzed. Cervical carcinoma (21.74%, 15/69) and thyroid cancer (21.74%, 15/69) were the most common types of cancer. Most cancers were diagnosed in SLE patients with an age 40~50 years. The disease duration of SLE was from 60~120 months. SLE patients without cancers were usually diagnosed between 20~30 years with duration of symptoms less than 12 months. As to the previous treatment of SLE, the uses of glucocorticoid, cyclophosphamide, methotrexate and azathioprine were comparable between patients with cancers and without (P>0.05). However, the use of hydroxychloroquine was more frequent in SLE patients than in patients with cancers (P<0.01). Correlation analysis revealed significant correlation between disease course of SLE (OR=4.25, 95%CI 1.79~10.01,P<0.001), hydroxychloroquine (OR=0.26, 95%CI 0.12~0.59,P<0.001) and cancer risk. Long disease course may be a risk factor for SLE patients to develop cancer, whereas hydroxychloroquine could be a protective factor.