The therapeutic efficacy of antiviral therapy against chronic viral infections and anticancer strategy against cancers is not satisfactory. Most of the antiviral drugs cause reduction of viral replication in chronic virus-infected subjects, however, recovery or cure from diseases does not occur in most cases. Various types of therapeutic approaches, such as ablation of cancer tissues, use of anticancer drugs and radiation therapy, are applied to treat patients with cancers. But, recurrence of cancer is a formidable problem in clinics. Taken together, sustained control of virus replication in chronic viral carriers and control of cancer recurrence in cancer patients are two major challenges. It is now evident that although different factors are responsible for pathogenesis of chronic viral infections and cancers, almost all patients exhibit distorted antiviral and anticancer immune responses. Thus, a new field of treatment of these diseases by immune intervention has been emerged. Immune therapy against chronic viral infections and cancers are in their infancy and facing several challenges. These challenges will be discussed to provide a road map for development of clinically-acceptable and potent immune therapeutic approaches against these diseases, especially in the context of liver diseases.