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Abstract Background This article is the first report of laparoscopic major hepatectomy of Hepatocellular carcinoma (HCC) following optimized portal vein embolization (oPVE). Case presentation The patient was diagnosed with a single 3 × 3.5 cm HCC located in segment 5 and 8 detected by enhanced computed tomography and magnetic resonance imaging. The lesion was adjacent to the right anterior and posterior portal veins, making it difficult to confirm the adequate liver functional remnant volume, surgical margin and R0 resection. In addition, the liver cirrhosis induced by a long history of chronic hepatitis B virus increased the potential risk of postoperative liver failure and refractory ascites. Therefore, we conducted a laparoscopic surgery following oPVE, by which the safe tumor margin was ensured and the outcome of the surgery was improved. The patient was discharged on the seventh day after the surgery. The AFP gradually decreased to a normal level during the 90-day follow-up. Conclusion This case report demonstrates that, in experienced hands for selected patients, laparoscopic hepatectomy after portal vein embolization is feasible and may be an alternative to open liver resection.