Background: A lack of effective diagnosis methods for preclinical HCC has resulted in a low rate of early detection. Aldo-keto reductase family 1 member B10 (AKR1B10) is associated with several cancer types. Objective: The association of AKR1B10 with HCC and the probability of its clinical utility for prognosis of HCC after treatment. Methods: A cross sectional study was conducted on 120 subjects who were divided into group I included 40 patients with HCC, group II included 40 patients with CLD and group III included 40 apparently healthy subjects. All patients were subjected to complete history taking an d thorough clinical examination. Complete blood picture, liver enzymes, serum bilirubin, S. albumin, INR, S. creatinine, S. AFP and S. AKR1B10 by ELISA were done. AKR1B10 was done before and one month after HCC ablation. Pelvi-abdominal ultrasonography, multislice CT scan and/or dynamic MRI were done. Patients with HCC were treated by TACE and RFA. Results: There is a statistically significant decrease of AKR1B10 after treatment in improved and failed cases. ROC curve analysis for AKR1B10 before treatment is good in differentiating between HCC and CLD groups (AUC=0.728) at a cut off level is 2834.5. There is a statistically significant decrease of AFP from before to after treatment is detected for HCC group. Conclusion: AKR1B10 is good for diagnosis of HCC and could be used as a novel screening method and the diagnostic efficacy of HCC is more when combined with AFP.