To explore the clinical characteristics of xanthogranulomatous cholecystitis (XGC), improve the accuracy of preoperative diagnosis, and optimize diagnostic and therapeutic strategies. Methods    A retrospective analysis was conducted on the clinical data of 110 XGC patients and 110 gallbladder cancer (GBC) patients admitted at Third Affiliated Hospital of Naval Medical University（Shanghai Eastern Hepatobiliary Surgery Hospital） between January 2018 and December 2022. Data collected included general information, clinical presentations, imaging findings, preoperative diagnoses, and treatment processes. The characteristics of the two groups were compared, and intraoperative and postoperative pathological results were summarized. Results    The mean age in the XGC group was (60.7±10.0) years old, with a male-to-female ratio of 2.4∶1. The accuracy of preoperative diagnosis for XGC was 8.2% (9/110), while 40.0% (44/110) of cases were misdiagnosed as GBC. The positive diagnostic rate of intraoperative frozen section pathology was 85.5% (71/83), and the postoperative pathological confirmation rate reached 100%. Imaging characteristics included nodules within the gallbladder wall, diffuse thickening of the gallbladder wall, an intact mucosal line, and the “layered sandwich sign” on contrast-enhanced scans. Compared with the GBC group, the XGC groups showed no statistically significant difference in elevated CA19-9 levels (P=0.281) but a statistically significant difference in elevated CEA levels (P<0.001). In surgical treatment, 43 patients underwent cholecystectomy, with a conversion rate from laparoscopic to open surgery of 41.2%. Open cholecystectomy did not significantly increase operative time (P>0.05), but it was associated with a longer hospital stay compared to laparoscopic surgery (P<0.05). The postoperative complication rate was 14.5% (16/110), including abdominal bleeding, bile leakage, and wound infections. Conclusion    XGC is a benign disease that often is preoperatively misdiagnosed as GBC, leading to unnecessary surgical extensions. The characteristic imaging findings of XGC are critical for preoperative diagnosis. For patients suspected of having XGC, laparoscopic surgery should be carefully selected, and routine intraoperative frozen section pathology is recommended to exclude malignancy. Patients with confirmed XGC have a favorable prognosis, but attention should be paid to preventing postoperative complications, with targeted measures implemented to reduce postoperative risks.