Aim of the study: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related fatalities worldwide. The burden of HCC incidence in Egypt has doubled in the last 10 years. The primary aim of this research was to assess the safety and efficacy of autologous dendritic cells (DCs) generated from peripheral blood. Material and methods: This trial was carried out at the Sohag Center of Cardiac and Digestive System. Patients with HCC were grouped into two groups (control group and DC injection group). The study group received intradermal autologous DCs twice weekly for three weeks, with a total of six vaccinations of 0.7 IU, whereas the control group received conservative treatment. Results:The study group showed statistically significant clinical improvement in the Child-Pugh score and overall survival. Laboratory evaluation revealed a significant reduction of a-fetoprotein, from 232 ng/dl at baseline to 193 ng/dl after 3 months to 153 ng/dl after 6 months, in the injection group, as compared with the control group, which increased from 228 ng/dl at baseline to 269 ng/dl at 3 months to 305 ng/dl at 6 months. Also, liver function improved significantly at both 3 and 6 months in the injected group compared with the control group. Regarding lymphocyte subsets, T-cytotoxic lymphocytes (CD8 + ) and natural killer cells (CD56+ve) increased significantly in the injection group. Conclusions: DC injection may be effective treatment of patients with advanced HCC to improve quality of life.