Gallbladder cancer (GBC) is the most common cancer of the biliary tract, constituting 80%-95% of malignant biliary tract tumors. Surgical resection is currently regarded as the sole curative treatment for GBC. Hepatopancreatoduodenectomy (HPD) has been adopted to remove the advanced gallbladder tumor together with the infiltrated parts within the liver, lower biliary tract and the peripancreatic region of GBC patients. However, patients who underwent HPD were reported to have a distinctly higher postoperative morbidity (71.4%, ranging from 30.8% to 100%) and mortality (13.2%, ranging from 2.4% to 46.9%) than those given pancreatoduodenectomy (PD) alone. We present two patients with advanced GBC who underwent a modified surgical approach of HPD: PD with microwave ablation (MWA) of adjacent liver tissues and the technique of intraductal cooling of major bile ducts. No serious complications like bile leakage, pancreatic fistula, hemorrhage and organ dysfunction, etc. occurred in the two patients. They had a rapid recovery with postoperative hospital stay being 14 days. Application of this approach effectively eliminated tumor-infiltrated adjacent tissues, and maximally reduced the postoperative morbidity and mortality. This modified surgical method is secure and efficacious for the treatment of locally advanced GBC.