Objective To investigate the effect of combined treatment of percutaneous transhepatic cholecystectomy and endoscopic cholecystectomy in elderly patients with moderate acute cholecystitis. Methods The research objects were 60 elderly patients with moderate acute cholecystitis, grouping according to random number table method, the control group of 30 cases were treated with selective endoscopic cholecystectomy, the observation group of 30 patients were treated with the percutaneous liver gallbladder puncture drainage on the basis of selective endoscopic cholecystectomy. Statistical analysis of humoral immunity, cellular immunity, ALP, TBIL, IBLL levels before and after operation, AMY, white blood cell count, VAS score and complications were conducted. Results The levels of ALP, TBIL, IBLL, AMY, WBC count, VAS score and complications in the observation group were lower than those in the control group. The indexes of humoral immunity and cellular immunity in the observation group were higher than those in the control group (P<0.05). Conclusion Endoscopic cholecystectomy used in the treatment of elderly moderate acute cholecystitis combined on the basis of percutaneous transhepatic gallbladder puncture drainage can improve curative effect, reduce the risk of selective endoscopic cholecystectomy, help patients with postoperative recovery, also can reduce the patient's immune function damage, improve the humoral immunity indexes, relieve pain, reduce the incidence of complications, which has high application value.