A series of new pyrazolothiazole hybrids were designed and synthesized by the microwave‐assisted multicomponent reaction of thiosemicarbazide, 3‐(furan‐2‐yl)‐1‐(pyridin‐2‐yl)prop‐2‐en‐1‐one and 1‐(pyridin‐2‐yl)‐3‐(thiophen‐2‐yl)prop‐2‐en‐1‐one with substituted 2‐bromoacetophenones. Structures of all the synthesized compounds were in good agreement with their spectral (FTIR, ¹H & ¹³C NMR, Mass) and analytical data (CHN analysis). The target compounds were screened for their in vitro cytotoxic activity by testing against human adenocarcinoma (A549), cervical cancer (HeLa), human neuroblastoma (SK−N‐SH) and human prostate cancer (DU‐145) cell lines. From the in vitro results, it was found that the compound derived from p‐ NO₂ phenyl (4 h) has potent activity against HeLa cell line with IC₅₀ value 9.97 ± 0.05 μM. Also, the compounds having p‐OCH₃ phenyl (4 c), phenyl (4 i), and p‐Cl phenyl (4 j) substitutions exhibited significant activity against HeLa cell line with IC₅₀ values 19.78 ± 0.03 μM, 18.47 ± 0.01 μM and 15.61 ± 0.06 μM respectively.