Squamous cell carcinoma (SCC) of the liver is rare, and is more commonly found in the skin, rectum, cervical or inguinal lymph nodes.A 73-year-old man had been experiencing right upper quadrant discomfort for some weeks. He had a 50-year history of smoking and drinking. On average, he smoked 20 cigarettes and consumed 200 galcoholdaily. He didn't have a history of hepatitis or surgery. Fever, vomiting, jaundice, dysuria, chills, and abdominal distention were not observed at the time of admission. Tenderness in the right upper quadrant was found on physical examination, but there was no palpable abdominal mass. No obvious abnormalities in laboratory tests and tumor markers were found. The plasma retention rate of indocyanine green (ICG) at 15 min was 1.35%. Subsequent abdominal ultrasonography showed a mixed echoic mass approximately 3.8 cm diameter in the left caudate lobe of the liver. Abdominal computed tomography confirmed a 3.0 cm × 3.5 cm irregular mass with inhomogeneous density and moderate delayed enhancement in the left caudate lobe of the liver. Laparoscopic left caudate lobectomy was performed to remove the liver mass. Intra-operative findings confirmed a non-cirrhotic liver, with a 3 cm × 3.5 cm white tumor mass in the left caudate lobe with no tumor rupture and no hemoperitoneum. The resection margin was 1.0 cm in width.We describe the first case of SCC in the left caudate lobe of the liver, which was successfully treated by surgical resection and postoperative immunotherapy. No tumor recurrence was observed during the 8-mo follow-up.©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.