Surgeons can achieve successful resection in patients with hepatocellular carcinoma and portal vein tumor thrombus despite resistance to first-line therapy.

• A patient responded to second-line therapy with notable reduction in tumor size and portal vein thrombus, allowing for laparoscopic surgery.
• The procedure took 340 minutes with minimal blood loss (100 ml) and resulted in extensive necrosis of the tumor.

This case underscores the importance of individualized treatment strategies in complex cases, improving surgical candidacy.

• The patient remains recurrence-free after subsequent targeted therapies.