Breast cancer is the most common cancer in females, and the leading cause of cancer-related mortality in the world. Among the available treatment options for cancer, chemotherapy is the therapy for treating a variety of cancer patients. However, the therapeutic efficacy of current agents is minimal and these drugs do not retard the progression of disease pathology. Lack of appropriate therapy may increase the prevalence of disease in world. Hence, more effective strategies and novel therapies must be pursued for altering the progression of the disease acting through different mechanisms. There is a continuing need for new and improved therapy. Hence, Vitamin B17 is suggested a therapeutic potential for treating breast cancer. This study is to evaluate the potential therapy of vitamin B17 (Vit B17, amygdalin) against Ehrlish solid tumors, bearing mice (EST) induced DNA damage, NF-Kb, TNFa and apoptosis. Sixty female mice were randomly divided into four groups: (I, control group; II, VitB17 group; III, EST group; IV, EST+VitB17 group). EST induced group had elevated in the levels of serum ALT, AST, ALP, creatinine, urea, potassium ions, cholesterol, triglycerides, cytokine IFNγ, NF-kb, DNA damage, tumor TNF-α, VEGF expressions and had an associated reduction in serum albumin, total proteins, sodium ions, tumor NF-kb, Bcl2 and survivin expressions. Treatment of EST with vitamin B17 (EST+VitB17) modulates the changes in liver and kidney functions, electrolytes, cytokines, NF-kb and apoptosis in mice bearing EST. Hence, these findings suggest that vitamin B17 can be a reliable and novel therapy for breast cancer, further validate the neoplastic activity of Vitamin B17 as a potential therapy for other types of cancer is needed. © 2020 Pakistan Journal of Pharmaceutical Sciences. All rights reserved.