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Introduction and Importance: Non-viral hepatocellular carcinoma (HCC) is increasingly prevalent but often presents with atypical manifestations, creating diagnostic challenges in clinical practice, particularly when it mimics a liver abscess. Case Presentation: A 63-year-old man with a history of gastric cancer surgery (T2N0M0) presented with a hypoechoic liver lesion on ultrasound during follow-up. Laboratory tests revealed elevated liver enzyme levels (AST: 75 IU/L, ALT: 107 IU/L), a normal alpha-fetoprotein (AFP) level (3.2 ng/mL), a markedly elevated PIVKA-II level (595.0 mAU/mL), negative HBV-DNA, negative total hepatitis B core antibodies (anti-HBc total), negative Toxocara IgM result, and a positive Toxocara IgG result. Imaging studies suggested a liver abscess, but two consecutive liver biopsies showed only inflammation without malignant cells or parasites. Owing to a clinical–biochemical discrepancy and elevated PIVKA-II level, surgical resection was performed. Histopathological examination confirmed well-differentiated hepatocellular carcinoma with 40% tumor necrosis (pT1b according to AJCC criteria) in a non-cirrhotic liver. Clinical Discussion: PIVKA-II demonstrates superior diagnostic value compared with AFP, with marked elevation (595.0 mAU/mL) despite normal AFP levels. Extensive necrosis (40%) can create abscess-like imaging appearances, leading to negative biopsies due to sampling error. The absence of typical infectious symptoms combined with elevated PIVKA-II level should raise suspicion for malignancy despite atypical imaging. Conclusion: This case illustrates the diagnostic complexity of non-viral HCC presenting as a liver abscess. PIVKA-II demonstrates superior diagnostic value compared with AFP in non-viral HCC. Combined biomarker assessment and maintaining a high level of clinical suspicion are essential for accurate diagnosis of atypical HCC cases.