<p>We report a rare case of giant hepatocellular carcinoma (HCC) with direct invasion to the colon and synchronous multiple lung metastases that achieved complete remission with surgical hepatectomy followed by chemotherapy with atezolizumab and bevacizumab. An 80-year-old man presented with abdominal distension and appetite loss. Imaging studies demonstrated a large HCC protruding from the liver with compression and invasion of the ascending colon, accompanied by multiple bilateral pulmonary nodules. To relieve symptoms and reduce the risk of tumor rupture, upfront surgical resection consisting of right hepatectomy and right hemicolectomy was performed. Histopathological examination revealed moderately to poorly differentiated HCC with direct invasion into the ascending colon and microscopic portal vein invasion. Postoperatively, tumor markers initially decreased; however, subsequent elevation led to initiation of atezolizumab plus bevacizumab for treatment of pulmonary metastases. Tumor markers subsequently normalized, and follow-up computed tomography demonstrated disappearance of all pulmonary metastases, with only scar-like lesions remaining. Radiologic complete remission was achieved 14 months after hepatectomy. The patient remains alive without recurrence 54 months after surgery. Direct invasion of HCC into adjacent organs is extremely rare and is generally associated with poor prognosis. The role of systemic chemotherapy after reduction surgery for advanced HCC remains controversial. Although this is a single case experience and caution is needed when generalizing, this case suggested that combined treatment with initial resection of the primary tumor followed by immunotherapy for remnant lesions could be feasible in selected patients and would potentially contribute to symptom relief and control of metastatic lesions.</p>