In this report, a series of phenyl tagged isoxazole-benzoxadiazole hybrids 4a–4g were synthesized by substituting in phenyl ring C4’ with -OCH3, -CH3, -F, -Cl, -Br and C3’ with -NO2. Anticancer potential of 4a–4g on MDA MB-231 human cancer cell line was evaluated by using MTT assay. The order of anticancer activity of derived hybrids with phenyl ring substitution is, p-Br>p-Cl, p-F, m-NO2, p-CH3, >p-OCH3, parent hybrid. Among them, 4g; hybrid with p-Br exhibits highest anticancer behavior. The reported haptophoric hybrids may provide a useful insight for designing effective chemotherapy drugs for treating MDA MB 231 cancer cells.