The study aimed to develop an amphoteric hyaluronic acid (HA) derivative with polyethyleneimine (PEI) chains (HAP) for gene delivery to overcome the disadvantages of PEI as gene carrier including the cytotoxicity caused by excess of positive charge, non-special interaction and aggregation in the blood, and non-target gene delivery.The HAP was synthesized by an imine reaction between periodate-oxidized HA and PEI.The HAP/DNA complex was prepared, and its characterization was investigated.