Objective: To investigate the clinical and serological features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) overlap syndrome (Rhupus syndrome). Methods: We retrospectively reviewed the medical records of 21 patients with Rhupus syndrome who were hospitalized at Department of Rheumatology and Immunology, People’s Hospital of Xinjiang Uygur Autonomous Region between January 2010 and January 2018. We compared the joint involvement, autoantibodies and clinical manifestations of Rhupus syndrome with 81 cases of RA-alone and 51 cases of SLE-alone. Results: In 21 patients with Rhupus syndrome, there are 3 males and 18 females. Compared with the SLE-alone group, the patients with Rhupus syndrome were older [(49.43±11.66) vs. (40.59±12.73), P=0.008]. The median age of the patients with Rhupus syndrome at RA onset was significantly younger than that of the RA-alone patients [(32.58±11.14) vs. (43.11±11.83), P=0.010]. Of the 21 patients with Rhupus syndrome, the initial diagnosis was RA in 57% (12/21), except 2 male patients, the other 10 patients with SLE manifestations were menopause, the mean age of amenorrhea or menopause was (44.30±5.33) (36-50) years. The mean interval between the onset of SLE and RA was 10.83 years. Two patients started with SLE manifestations. Moreover, both diseases simultaneously developed in 33.3% of the patients. Except one male patient, 3 patients were in menopause stage when RA and SLE appeared. The positive rate of specific antibody Rhupus syndrome was similar to that of RA. Renal damage was relatively rare in SLE related manifestations, but the incidence of interstitial lung disease was higher. There were no significant differences in the prevalence of complements C3 and C4, antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), anti-SSA or anti-SSB antibody between the Rhupus syndrome and SLE-alone group. Conclusion: Rhupus syndrome is an overlapping syndrome in which RA and SLE coexist. Most of the diseases occur in RA and the related manifestations of RA are more serious than those of SLE. The incidence of Rhupus syndrome may be related to the change of sex hormone levels.