Hepatocellular carcinoma(HCC)often develops in patients with underlying liver disease,yet HCC with syncytial giant cells(SGCs)is extremely rare.Herein,we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein.Clinical examination and imaging analyses revealed a tumor-like lesion in segment 4 of the liver,which was removed by limited wedge resection.Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules,with some SGCs,embedded within the boundaries of the neoplastic lesion.The adjacent liver parenchyma showed microvesicular steatosis,pericellular fibrosis,and moderate hemosiderin accumulation(grade 2,as determined by Prussian blue iron stain)in hepatocytes and Kupffer cells but no copper accumulation(as determined by orcein stain).Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs.The diagnosis was made for cirrhosis-related HCC with SGCs.The previous reports of pleomorphic HCC have featured osteoclast-like(i.e.,mesenchymal type)giant cells,making this case of epithelial type giant cells very rare.The patient’s 6-month history of hypericum perforatum/St John’s wort self-medication may have prompted the cirrhosis or HCC progression or the unusual SGC manifestation. Hepatocellular carcinoma (HCC) often develops in patients with underlying liver disease, yet HCC with syncytial giant cells (SGCs) is extremely rare. Herein, we report a 55-year-old man with a 6-year history of alcoholic cirrhosis who during his regular checkup presented with marked elevation of alpha-fetoprotein. Clinical examination and imaging analyzes revealed a tumor-like lesion in segment 4 of the liver, which was removed by limited wedge resection. Histological analysis by hematoxylin and eosin staining indicated pleomorphic and atypical nodules, with some SGCs, embedded within the boundaries of the neoplastic lesion. adjacent liver parenchyma showed microvesicular steatosis, pericellular fibrosis, and moderate hemosiderin accumulation (grade 2, as determined by Prussian blue iron stain) in hepatocytes and Kupffer cells but no copper accumulation ( as determined by orcein stain). Immunohistochemical analysis showed hepatocyte antigen-positive staining for the neoplastic cells and SGCs.The diagno sis was made for cirrhosis-related HCC with SGCs.The previous reports of pleomorphic HCC have featured osteoclast-like (ie, mesenchymal type) giant cells, making this case of epithelial type giant cells very rare. The patient’s 6-month history of hypericum perforatum / St John’s wort self-medication may have the cirrhosis or HCC progression or the unusual SGC manifestation.