Objective To explore the feasibility of single incision laparoscopic cholecystectomy in the treatment of acute cholecystitis, and to provide evidence based medicine for clinical treatment. Methods A total of 160 cases of acute cholecystitis who received treatment in our hospital from Jan. 2012 to Dec. 2015 were randomly divided into single incision group (n=80, received single incision laparoscopic cholecystectomy) and three incisions group (n=80, received three incisions laparoscopic cholecystectomy). The clinical and laboratory indexes were compared between the 2 groups. Results Compared with the three incisions group, there were statistically significant differences in the operation time, incision pain score, and subjective satisfaction, which were better in single incision group (P<0.05). But there was no significant difference in the blood loss, bed time, anal exhaust time, recovery time of intestinal peristalsis, hospitalization time, incidence of complication (including abdominal infection, bile duct injury, biliary fistula, and incision infection), ratios of T cell subsets (including CD3, CD4, and CD8 T cell), levels of immunoglobulin (including IgA, IgG, and IgM), and level of C reactive protein (P>0.05). Conclusions The effectiveness of single incision laparoscopic cholecystectomy is as good as three incisions laparoscopic cholecystectomy, but this single incision laparoscopic surgery is difficult, and its indications should be cautious. Single incision laparoscopic cholecystectomy is more suitable for patients undergoing elective cholecystectomy.