TiO2-based metal oxide affinity chromatography (MOAC) nanomaterials show high potential in phosphoproteome mass-spectrometric (MS) analysis. However, a drawback of TiO2 nanomaterials is poor water solubility, which greatly reduces the enrichment efficiency of phosphopeptides and eventually limits their use in phosphoproteome MS analysis. In this work, a hydrophilic TiO2 hybrid material (denoted as NH2@TiO2) is successfully designed with 1,6-hexanediamine modified on the surface of TiO2 nanoparticles and applied as a biofunctional adsorbent for selective enrichment of phosphopeptides. The novel TiO2 hybrid material with high hydrophilicity and biocompatibility is characterized using scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and infrared (IR) spectroscopy, and its performance in selective enrichment of phosphopeptides is evaluated with the standard protein digests, human serum and the tryptic digests of nonfat milk.