Lymphoma is one of the lethal tumors affecting lymphoid tissues in the body. Its treatment has been challenging because the complex pathology, resistance to the drugs, side effects with existing chemo and radiation therapies. Natural compounds are gaining interest in treating these kind of tumors as they are relatively safer and effective in controlling the tumor burden. Emodin is one of such a plant derived natural compound with potential anti-cancer/tumor properties. We have evaluated the therapeutic efficacy of emodin as an anti-lymphoma drug in reducing tumor burden in vivo in the Swiss Albino mice induced with Dalton Ascitic lymphoma (DAL). The findings have been compared with a standard anti-cancer drug methotrexate. Our findings show that the emodin controlled the tumor burden in DAL bearing mice. Furthermore, the in-silico analysis has shown that emodin as a potential drug candidate for lymphoma based on the Lipinski’s rule of 5 and molecular docking studies.