BACKGROUND The main cause of death in patients with hepatocellular carcinoma (HCC) with portal hypertension is esophageal and gastric variceal bleeding caused by severe portal hypertension; therefore, the treatment of portal hypertension is particularly important to prolong the survival of patients. The therapeutic efficacy and safety of transarterial chemoembolization (TACE) combined with a transjugular intrahepatic portosystemic shunt (TIPS) for HCC with esophageal and gastric variceal bleeding has been rarely reported. The aim of this study was to analyze the clinical efficacy of TIPS combined with TACE in the treatment of HCC with esophageal and gastric variceal bleeding. MATERIAL AND METHODS A total of 80 patients with HCC with esophageal and gastric variceal bleeding from July 2015 to November 2019 were retrospectively investigated. Clinical outcomes, biochemical indexes, and complications were compared between TIPS plus TACE and endoscopy plus TACE treatments. RESULTS Gastrointestinal rebleeding and adverse reactions (P<0.05) after TIPS combined with TACE were lower than that after endoscopy combined with TACE treatment. Furthermore, TIPS plus TACE had superior clinical outcomes than endoscopy plus TACE, which was associated with promising progression-free survival, overall survival, objective response rate, and disease control rate, and improved liver function. CONCLUSIONS TIPS combined with TACE was better than endoscopy combined with TACE in the treatment of patients with HCC and esophageal and gastric variceal bleeding. TIPS combined with TACE had a better therapeutic effect on improving liver function and prolonging patient survival time.