Introduction: The liver is known as a tissue highly sensitive to immunological changes such as cytokines activity. It has been shown that using selenium nanoparticle supplementation and exercise training separately can effectively decrease tumor volume and improve immune responses. The aim of this study was to examine the effects of aerobic interval training and supplementation of selenium nanoparticles on protein expression of cytokines in liver tissue in mice with breast cancer. Materials and Methods: Sixty-four Balbc mice were divided into eight groups. Experimental groups received aerobic interval training and selenium nanoparticles supplementation orally for 6 weeks, before and after cancer induction. At the end of the sixth week, after tumor injection, proteins levels of IL-6, IL-4, TNF-α and INF-γ were measured in liver tissue by the enzyme-linked immunosorbent assay (ELISA) method. Results: Results of the current study showed that IL-6, TNF-α and IL-4 protein levels decreased in liver tissue of the breast cancer tumor (P<0.05). Aerobic interval training caused significant increase in IL-6 and TNF-α protein levels in liver tissue (P<0.05). Increase in INF-γ cytokine levels in liver tissue was also observed, following selenium nanoparticle supplementation (P<0.05). Results also showed that tumor volume decreased following exercise training and administration of selenium nanoparticles administration. Conclusion: Cytokines changes in liver tissue occurred in conjunction with decrease in tumor volume. It is possible that simultaneously using selenium nanoparticles and exercise training with immune system reinforcement could help in reducing tumor volume and modulating cytokine levels in liver.