There is currently a great deal of interest in the chemistry of pyrazol-5-ones and their related compounds due to their wide range of biological and pharmacological activities. A variety of compounds having a pyrazol-5-one moiety as a structural unit have been synthesized and studied with interest centered on their potential pharmaceutical activity. Previous researches revealed that pyrazol-5-one moiety is an important pharmacophore which exhibits outstanding biological activities such as antioxidant, anti-fungal, antibacterial, antidepressant, anticonvulsant, anti-inflammatory, antipyretic and antitumor. The present work focused on studying the synthesis of novel pyrazoline derivatives and screening of some selected their antiproliferative potency of some selected derivatives namely compounds 1, 2, 3, 4, 5, 6, 7, 8 and 9 towards hepatocellular carcinoma cell line (HEPG2). Results indicated that the selected compounds 9, 7 and 6 were the most active derivatives towards HEPG2 cell line with IC50 equals 3.74, 3.92 and 4.31µg/mL respectively. The newly prepared selected derivatives showed interesting antiproliferative potency in comparison to the traditional anticancer drugs: 5 Fluorouracil and doxorubicin. However, the potent compounds needs more pharmacological and preclinical studies.