A series of fluorophenylpyrazole-picolinamide derivatives were synthesized in high yields using a cross-coupling reaction catalyzed byin situformed palladium-N-heterocyclic carbenes (Pd-NHCs). The synthesized novel derivatives were evaluated forin vitroanticancer activity against a panel of four human tumor cell lines, HeLa (cervical), A-549 (lung), MCF-7 (breast), and IMR-32 (neuroblastoma). Four compounds,11c,11e,11j, and11k, showed growth inhibition (low mu M) comparable with the standard drug cisplatin, providing a preliminary structure-activity relationship for the series. The present procedure is operationally simple and works with a wide range of substrates and may thus be useful in further compound optimization.