Abstract Three series of novel 1,3,5‐trisubstituted 2‐pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized. The in vitro antitumor activity of the obtained compounds was determined at the National Cancer Institute (NCI). The 5‐(benzo[ d ][1,3]dioxol‐5‐yl)‐3‐(4‐methoxyphenyl)‐4,5‐dihydro‐1 H ‐pyrazole‐1‐carbothioamide ( 9a ) is the most prominent of the compounds due to its remarkable activity toward leukemia (RPMI‐8226), renal cancer (UO‐31) and prostate cancer (DU‐145) cell lines with GI 50 values of 1.88, 1.91 and 1.94 µM, respectively.