In this work, covalently bonded folic acid and niobium substituted Wells–Dawson polyoxometalate, (Bu₄N)₅H₄[P₂W₁₅Nb₃O₆₂]-folic acid, has been synthesized and characterized. Afterward, the bioactivity behavior of this hybrid compound against cervical (HeLa) and human breast (MCF-7) cancer cells, and also human fibroblast cells (HFB) was investigated. This intelligent hybrid compound could surprisingly knock down cancer cells (IC50 about 37, 49 and 110 μg mL⁻¹ on HeLa, MCF-7 and HFB, respectively). A higher expression of folic acid on HeLa and MCF-7 cells could explain the greater cytotoxicity of this hybrid polyoxometalate. As folate receptor (FR) negative cells, the normal cells remained approximately 2- to 3-fold safer. The bioactivity effect of (Bu₄N)₅H₄[P₂W₁₅Nb₃O₆₂] on HeLa and MCF-7 cells reaches IC-50 values of about 87 and 107 μg mL⁻¹ respectively, which is about twice that of the as synthesized hybrid compound. Compared to methotrexate as a positive control, this hybrid polyoxometalate is about 2 to 3 times safer on healthy cells. Moreover, it has high potential for developing a selective therapeutic effect against FR-positive cancer cells.