Introduction: Hepatocellular carcinoma (HCC) is the commonest type of primary liver cancers, and most patients are diagnosed in advanced or terminal stages with poor prognosis. Therefore, it is crucial to establish new clinical markers for early HCC diagnosis and staging. Aim: Our study aimed to evaluate carbonic anhydrase IX (CA9) as an early serum biomarker for HCC diagnosis within cirrhotic Egyptian patients. Material and methods: Fifty-eight cirrhotic patients and sixty HCC patients as well as fifty-eight healthy control subjects were selected for the current study. Routine liver tests, CBC, C-reactive protein, alpha fetoprotein (AFP) and serum CA9 were done for all the patients included. Results: Serum CA9 and AFP levels increased significantly in HCC and cirrhotic patients compared to controls. CA9 increased with the development of hepatic disease through the direct proportion of CA9 with BCLC staging, child classification, ascites and encephalopathy in HCC cohort and the direct proportion with child classification and ascites in cirrhotic cohort. Our findings showed that CA9 has higher accuracy than AFP to differentiate between HCC (at cutoff value>85 pg/mL) or cirrhotic patients (at cutoff value>54.7 pg/mL) and control with greater sensitivity and specificity than AFP. On the other hand, CA9 showed lower sensitivity and specificity than AFP in discrimination between cirrhosis and HCC only 51.67% and 46.55%, respectively. Conclusions: CA9 could be used as biomarker for early HCC diagnosis and that there is strong relationship between CA9 level and HCC worse prognosis suggesting its potential role in HCC development and disease progression.