Parabens, which are hydroxybenzoic acid esters, are particularly used as protective against mold andfungus. Ethyl paraben is a compound open to modification for the synthesis of new molecules due to the ester group inits structure. In this study, ethyl paraben was used as a starting material. A new series of novel hydrazide-hydrazonesfrom derived ethyl paraben were synthesized and characterized by spectroscopic techniques such as NMR, FT-IRbesides elemental analysis. In order to determine the anticancer activity of the aimed ethyl paraben hydrazidehydrazones we evaluated their cytotoxic activity on liver cancer cell line liver hepatocellular carcinoma (HepG2). Hereinwe described several 4-hydroxy-N'-[substituted methylidene] benzohydrazides (3a-j) as anticancer agents. Wedesigned, synthesized and characterized the series of novel hydrazide-hydrazones from ethyl paraben. All of thecompounds evaluated for anticancer activity by using MTT assay for 24 and 48 h. mRNA transcription levels of Bax,Bcl-2 and caspase-3 genes were determined by realtime polymerase chain reaction (qRT-PCR) analysis. Compounds 3iand 3j showed anticancer activity with 42.4 and 37.4 µM IC50 values, respectively. Doxorubicin was used as a positivesensitivity reference standard. qRTPCR analysis approved that there was a timedependent rise in the expression levelsof Bax, Bcl-2 and Caspase 3 on apoptosis. The activities of the synthesized compounds changed depending on the doseand time of treatment and some of the molecules started to show activity within 48 hours.