There is no consensus of treatments for acute acalculous cholecystitis with systemic lupus erythematosus (SLE). The study was aimed to investigate the effect of the corticosteroid for these patients.A series of patients who were diagnosed as acute acalculous cholecystitis with SLE in the period from January 2012 to December 2016 at our hospital were included. They accepted 2 different conservative treatment strategies initially: the treatment using moxifloxacin (the antibiotic group), and the treatment using corticosteroid combined moxifloxacin (the corticosteroid group). Then clinical manifestations, laboratory features, and outcomes were analyzed.The study identified 22 women Han Chinese patients with the SLE history of 2.8 ± 1.4 year. There was no significant difference in SLE history, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2000), Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR), hematologic examination results, and corticosteroid dosage between 2 groups. And there was no significant difference in the symptom of acute cholecystitis, duration of the symptoms, white blood level, and the thickness of gallbladder wall between 2 groups either. However, the SLEDAI-2000 of the corticosteroid group was lower than that of the antibiotic group (7.3 ± 1.4 vs 10.7 ± 3.0, P = .03), so was the SLICC/ACR (0.1 ± 0.3 vs 0.3 ± 0.5, P = .01). Moreover, total 11 of 12 patients were successfully treated in the corticosteroid group, only 1 patient got cholecystectomy because no improvement after conservative treatment. While 4 of 10 patients were successfully treated by moxifloxacin alone, 6 patients had to accept cholecystectomy in the antibiotic group. The rate of successful conservative treatment in the corticosteroid group was higher than that of the antibiotic group (P = .02). All patients were followed up at least 6 months, there was no statistical difference in the rate of recurrence of abdominal pain between 2 groups (P = .37).The corticosteroid plays an important role in the management of the acalculous cholecystitis patient with SLE, and it should be considered as a first line of treatment.