OBJECTIVE According to the prevalence of neoplastic diseases, there is a deep necessity for discovery of novel anticancer drugs in the field of medicinal chemistry. In the current study, a new series of phenylthiazole derivatives (compounds 4a-4f) was synthesized and their anticancer activity was assessed in vitro. METHODS All synthesized derivatives were evaluated towards three human cancerous cell lines of SKNMC (Neuroblastoma), Hep-G2 (Human hepatocarcinoma) and MCF-7 cell (Breast cancer) using MTT assay and obtained values (IC50 ± SD) were compared with doxorubicin. RESULTS Unfortunately, none of the synthesized compounds showed superior activity than doxorubicin against cancerous cell lines. MCF-7 cell line was the most resistant cell line against tested compounds. Compounds 4c with para nitro (IC50 = 10.8 ± 0.08 µM) and 4d with meta chlorine (IC50 = 11.6 ± 0.12 µM) moieties exerted the highest cytotoxic effects towards SKNMC and Hep-G2 cell lines respectively. CONCLUSIONS A new series of phenylthiazole derivatives were synthesized and their anticancer activity was assessed against cancerous cell lines. More structural modifications and derivatization is necessary to achieve to the more potent compounds.