Background: Ablation therapy with advances in its techniques becomes widely used in patients with hepatocellular carcinoma. Ablative techniques can induce tumor cell death and stimulate many immunological responses. These responses can be evaluated through assessment of peripheral immune cells changes in systemic circulation. Aims: To investigate changes in the peripheral immune cells presented in CD4, CD8 and CD4/CD8 ratio after HCC ablation by different procedures and their relations to ablation result. Subjects and Methods: This study investigated 73 HCC patients admitted to Department of Tropical Medicine, Mansoura University Hospital, Egypt. The patients were stratified into three groups according to ablative technique used. Radiofrequency ablation was performed for 24 cases, microwave ablation for 24 and transarterial chemoembolization for 25 cases. After history taking, clinical examination, basic investigations, triphasic abdominal computerized tomography before and 4 weeks after the treatment, HCC patients were selected according to EASL guideline. Lymphocyte subset assay using flow cytometry 1 day before, and 4 weeks post ablation was done. The patients subdivided into successful and unsuccessful subgroup according to the result of ablation by CT. Results: In patients treated with Radiofrequency ablation, significant increase in CD4 count and CD4/CD8 ratio after treatment (P<0.001), while CD8+ cells count significantly decreased (P<0.002). In HCC patients treated with microwave ablation, CD4+ count and CD4/CD8 ratio significantly increased after treatment (P<0.001,<0.007), without significant differences in CD8+ cells count. After transarterial chemoembolization, CD4+ cells count and CD4/CD8 ratio significantly decreased (P<0.001) with significant increase of CD8+ cells (P<0.001). Changes in CD4, CD8, and CD4/CD8 ratio remained comparable to that occurred in both successfully ablated and cases with residual tumor. Conclusion: Various ablation procedures of HCC are associated with significant changes in peripheral T cell subpopulation. These changes mostly were due to the ablation of tumor cells but these changes cannot predict the success of ablation or recurrence of previously ablated one.