TiN coating has been demonstrated to improve the biocompatibility of bare NiTi alloys; however, essential biocompatibility differences between NiTi alloys before and after TiN coating are not known so far. In this study, to explore the underlying biological mechanisms of biocompatibility differences between them, the changes of bare and TiN-coated NiTi alloys in surface chemical composition, morphology, hydrophilicity, Ni ions release, cytotoxicity, apoptosis, and gene expression profiles were compared using energy-dispersive spectroscopy, scanning electron microscopy, contact angle, surface energy, Ni ions release analysis, the methylthiazoltetrazolium (MTT) method, flow cytometry and microarray methods, respectively. Pathways binding to networks and real-time polymerase chain reaction (PCR) were employed to analyze and validate the microarray data, respectively. It was found that, compared with the bare NiTi alloys, TiN coating significantly decreased Ni ions content on the surfaces of the NiTi alloys and reduced the release of Ni ions from the alloys, attenuated the inhibition of Ni ions to the expression of genes associated with anti-inflammatory, and also suppressed the promotion of Ni ions to the expression of apoptosis-related genes. Moreover, TiN coating distinctly improved the hydrophilicity and uniformity of the surfaces of the NiTi alloys, and contributed to the expression of genes participating in cell adhesion and other physiological activities. These results indicate that the TiN-coated NiTi alloys will help overcome the shortcomings of NiTi alloys used in clinical application currently, and can be expected to be a replacement of biomaterials for a medical device field.