In HCC, the tumor marker alpha-fetoprotein (AFP) is increased, but it might be normal in 40% of cases. Increased AFP implies worse tumor differentiation. This study aimed to clarify and determine the correlation between the histological differentiation grade of HCC and serum AFP level in patients managed at the RSCM (Dr. Cipto Mangunkusumo Hospital). In total, 32 of HCC cases of patients who underwent hepatectomy at RSCM in 2010-2016 were enrolled in a retrospective study. The subject characteristics, AFP levels, and histological differentiation grade were the variables analyzed in this study. A P value of <0.05 was considered to be significant. Among the subjects, 59.4% were HBsAg-positive and 12.5% were anti-HCV-positive. The tumor size was more than 5-10 cm in diameter in 50% subjects; 50% subjects were cirrhotic and 68.8% subjects had microvascular invasion. Overall, the AFP levels ranged from 0.5 to 400000 ng/mL (mean, 20183 ± SD 75580.08). The histological grade was well differentiated in 12.5%, moderately differentiated in 28.1%, and poorly differentiated in 59.4%. In cases with poorly differentiated HCC, the AFP level was <20 ng/mL in 42.1% and >20 ng/mL in 57.9%. Correlation analysis revealed an r value of 0.203 (P > 0.05). There was no correlation between the serum AFP level and histological differentiation grade of HCC. © 2018 Institute of Physics Publishing. All rights reserved.