Hepatoma is reported as one of the most common types of cancer associated with mortality worldwide. Several studies have suggested a possible correlation between MHC class-I polypeptide-related chain A (MICA) gene polymorphism and the susceptibility to develop hepatic cirrhosis induced-HCC. This study aimed to explore the predictive value of MICA gene polymorphism for the incidence of HCC on top of liver cirrhosis. A case-control study on patients selected from the outpatient Hepatology clinic, Specialized Medical Hospital, Mansoura University, Egypt, from January 2018 to August 2019. The incorporated patients were classified into sixty patients with hepatoma on top cirrhosis and twenty patients with liver cirrhosis. A restriction fragment length polymorphism identified the MICA gene polymorphism for all patients. This study revealed that HCC was more predominant in male patients, and 38.3% of total hepatoma patients had diabetes. Cirrhosis induced-HCC patients showed a significantly higher frequency of rs2596542 G/A genotypes of MICA gene than the non-malignant cirrhotic group (P<0.01). Additionally, the rs2596542 G/A genotype significantly increased risk of HCC (OR= 6.63, 95% CI= 1.65-26.64; P<0.01). The MICA rs2596542 polymorphism may be of value for predicting cirrhotic patients with a great susceptibility to developing hepatoma. Therefore, Cirrhotic patients with GA genotype of MICA are recommended to be closely followed up.