In the present study, the different contents of tantalum pentoxide (Ta2O5: 10, 15, 20 and 30 wt%) nanoparticles were introduced into the natural hydroxyapatite (nHA) coating structure on NiTi substrate through electrophoretic deposition (EPD) method. The phase compositions of coatings were perused before and after the sintering at 800 degrees C for 1 h by XRD. The incorporation of 30wt%Ta2O5 into nHA matrix induced the formation of undesirable soluble Ca-3(PO4)(2) phase in composite coating. The FESEM images showed that the density of continuous nHA coating increased by compositing with Ta2O5. The maximum adhesion strength of 28.3 +/- 0.7 MPa accomplished from the nHA-20 wt%Ta2O5 composite coating. The Ni ions concentration measurement results from the passivated-NiTi with nHA and nHA-(10, 15 and 20)wt%Ta2O5 coatings during 30 days of immersion in PBS clarified the positive role of Ta2O5 in decreasing the Ni leaching due to the lowering the open porosities of nHA structure. The biological response of the coating surfaces was assessed in vitro by cell culturing and MTS assay. By considering the morphology and density of adsorbed cells on each coating, the improved biocompatibility of nHA coating in the presence of Ta2O5 was justified by scrutinizing the surface roughness, wettability and charge. The highest cell attachment and proliferation on nHA-20 wt%Ta2O5 coating was related to owning the lowest roughness, wetting angle of 34 degrees +/- 0.5 and the highest negative surface charge density. Also, the concentration of the highest negative charge density on nHA-20 wt%Ta2O5 coating surface in the SBF solution caused to the enhancement of the amount of the apatite nuclei through providing more sites to calcium absorption.