Objectives: This is a randomized trial adopted to evaluate the safety and efficacy of immunization with specific anti-hepatocellular carcinoma dendritic cells (DCs) in Egyptian patients with advanced hepatocellular carcinoma (HCC) as a treatment or adjuvant therapy in comparison with the traditional therapy. Methods: This study was conducted on 20 HCC patients who were assigned to four groups according to BCLC staging; group I: HCC patients (stage B) received trans-arterial chemoembolization (TACE) and DCs as an adjuvant therapy; group II: HCC patients (stage B) received TACE only; group III: advanced HCC patients (stage D) received DCs vaccine; group IV: advanced HCC patients (stage D) received supportive treatment. DCs were generated from peripheral blood monocytes and pulsed with a lysate of an allogeneic hepatic cancer cell line (HepG2). Toxicity and immunological response were reported as primary outcomes whereas clinical biochemical and radiological responses were reported as secondary outcomes. Results: Our study detected that patients who received DCs vaccine (group III) showed mild decrease in Child-Pugh score as well as AFP and PIVKA II levels and developed 20% partial response [PR] 40% stable disease [SD] and 40% progressive disease [PD] compared to the patients of group IV on supportive treatment who developed 100% PD. Although group I patients developed PR (60%) SD (20%) and PD (20%) no significant difference was detected in the clinical biochemical or radiological response between group I and group II patients. DCs vaccine had minimal adverse effects with no autoimmunity and elicited a better immunological response such as increased CD8 cells percentage and number as well as decreased TGFβ levels in the vaccinated patients. Conclusion: DCs vaccine is safe as it is not associated with significant toxicity. However due to the small number of included patients the efficacy and immune response of using DCs vaccine in the treatment of advanced HCC patients need to be justified by testing of a large cohort.Keywords: Adjuvant; Dendritic cells; Hepatocellular carcinoma; Vaccine.