Background: In hepatocellular carcinoma (HCC), CK19 is a marker of hepatic progenitor cells and acts as a key player in tumor invasion, indicating poor prognosis. Early diagnosis of HCC heavily affects the clinical outcome of patients. The widely accepted serological marker for HCC diagnosis is alpha-fetoprotein (AFP). However, its diagnostic accuracy is controversial and unsatisfactory because of its low sensitivity. The objective of the current study is to evaluate the influence of CK19 level on Pattern of HCC in patients with liver cirrhosis. Patients and methods: This was a prospective case -control study that was conducted on patients attending at early detection of HCC Outpatient Clinic or admitted to Hepatology and Gastroenterology Unit, Specialized Medical Hospital Mansoura University, over past year. The current study included 75 participants divided into 3 groups: Group 1 (HCC), Group 2 (cirrhosis only) and Group 3 (healthy people without any medical disease). Results: There was statistically significant increase as regard median CK19 level, between degrees of aggressiveness index (A, B and C) (P >0.05). Regarding the validity of CK19 in differentiating the studied groups, there was no statistically significant difference as regard median CK19 level in cirrhosis and control groups with Sensitivity 56% and Specificity 40%. There was no statistically significant difference as regard median CK19 level in HCC and control groups with Sensitivity 64% and Specificity 40%. There was no statistically significant difference as regard median CK19 level in HCC and cirrhosis groups with Sensitivity 64% and Specificity 44%. There is weak significant relationship between the levels of CK19 and AFP in HCC cases (P-value 0.07). Conclusion: CK19 associated carry a poor prognosis as it associated with more aggressive pattern of HCC. CK19 is good negative marker of early HCC, So CK19 negative HCC patients has no priority for treatment.