Aim of the study We aimed to evaluate soluble CD25 (sCD25) as a marker for hepatocellular carcinoma (HCC) diagnosis. Material and methods Eighty-eight subjects were enrolled in our study in the years 2017-2018. They were divided into three groups as follows: group 1 – HCC group ( n = 44) patients, represented by BCLC stage A ( n = 16) patients, stage B ( n = 14) patients and stage C ( n = 14) patients for each stage. All HCC patients were on top of cirrhosis. Group 2 – group of cirrhotic patients without HCC ( n = 32); 50% of them were Child-Turcotte-Pugh class A ( n = 16) while class B was represented only by 43.7% ( n = 14) of patients. Group 3 – control group ( n = 12) of healthy subjects. Results The levels of sCD25 and AFP were higher in HCC patients than cirrhotic and control groups without a statistically significant difference between the three groups ( p -value > 0.05). For HCC presence, sensitivity and specificity of sCD25 were 86.4% and 29.5% respectively at a cut-off value of 1.1 × 10 3 pg/ml (AUC = 0.619, p -value = 0.054, PPV = 33.2%, NPV = 68.44%). For early detection of HCC, sCD25 had a sensitivity of 70.5% and a specificity of 30.9% at a cut-off value of 1.575 × 10 3 pg/ml (AUC = 0.577, p -value = 0.251, PPV = 58.5%, NPV = 43.1%), while the sensitivity and specificity of AFP were 75% and 62.5% respectively at a cut-off value of 9.5 ng/ml (AUC = 0.828, p = 0.000, PPV = 73.4%, NPV = 64.4%) in the same settings. Conclusions sCD25 seems to offer no better detection rate of HCC compared to AFP with lower sensitivity and specificity.