Abstract Background Hepatocellular carcinoma (HCC), a major health problem worldwide, is one of the most common primary neoplasms of the liver and one of the most common solid tumors in the world. More than 500,000 new cases were diagnosed each year. HCC accounts for between 85% and 90% of primary liver cancer. It is the fifth most common cancer worldwide and the third most common cause of cancer mortality. Aim of the Work The aim of this study is to assess of alpha fetoprotein in patients who are diagnosed with hepatocellular carcinoma after COVID-19 infection. Patients and Methods This is cross Sectional Study on 60 Egyptian patients with HCC presenting to multidisciplinary clinic during era of Covid 19 pandemic divided into two subgroups: Group I: 30 patients with HCC and COVID 19 infection and group II: 30 patients with HCC who weren’t infected with COVID 19. Results In this study we found that there was insignificant difference between both studied groups as regards age and sex (p = 0.92 and p = 0.119, respectively). In this study we demonstrated that there was insignificant difference between both studied groups as regards etiology of HCC (p > 0.05). In this thesis we cleared that there was highly significant difference between both studied groups as regards Liver presentations (P < 0.001). In this thesis we found that there was significant difference between both studied groups as regards CBC (p < 0.05). In this study we demonstrated that there was significant difference between both studied groups as regards liver function tests (p < 0.05). Our results showed that that there was highly significant difference between both studied groups as regards AFP (p = 0.002). In study in our hands, we found that there was highly significant difference between both studied groups as regards tumor size and tumor stage (p < 0.001). In this study we found that there was highly significant difference between both studied groups as regards MELD score (p < 0.001). In this study we illustrated that Child Pugh class, MELD score, AFP and COVID-19 infection were the independent risk factors associated with poor survival among HCC patients Conclusion Our study concluded that tumor marker parameters, including AFP, can be used as Prognostic tools for HCC patients with СOVID-19. In which there were higher mortality rate among HCC with COVID-19 with higher levels of AFP.