The aim of this study was to evaluate the effect of the hexyl acrylate conjugated polyamidoamine (PAMSM) dendrimer on different cell lines in the presence and absence of serum. Although the positively charged dendrimers including PAMAM has been considered as efficient gene carriers, their cytotoxicity is a major barrier for their clinical applications. The conjugation of hexyl acrylate on PAMAM dendrimer was carried out to improve the hydrophilic-hydrophiobic balance of the dendrimer as well as the modulation of the positive charge on the dendrimer structure. The cytotoxicity of PAMAM derivatives was evaluated using MTT test on HepG2, MCF-7 and A549 cell lines in the presence and absence of serum. The results revealed that the modified PAMAM dendrimers induced less toxic effects on the cell lines in the presence of serum. Therefore, conjugation of acrylate on the PAMAM structure could be an efficient way to reduce the dendrimer toxicity allowing the administration of more dendrimer for gene delivery.