A novel strategy for selectively adsorbing phospholipids (PLs) on titania-coated silica core-shell microspheres (TiO2/SiO2) was developed. The TiO2/SiO2 microspheres were prepared through water-vapor-induced internal hydrolysis and then characterized by SEM, UV-vis spectroscopy, X-ray diffraction, and measurements of Brunauer-Emmett-Teller surface area. Analyses showed that the titania layer was uniformly distributed onto the surface of silica particles. The TiO2/SiO2 microspheres were employed as sorbent in solid-phase extraction (SPE), and their absorptive ability was investigated by reversed-phase liquid chromatography-evaporative light scattering detection (RPLC-ELSD). Important factors that affect the extraction, such as loading buffer, eluting buffer, and elution volume, were investigated in detail and optimized by using standard samples. Results reveal that the developed SPE approach had higher recoveries for PLs than that based on pure TiO2 particles. The proposed SPE method was used for extraction of PLs from serum and showed great potential for identifying more kinds of endogenous PL metabolites by ultra performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF MS). The proposed SPE method with the composite sorbent was used to screen PLs from a biological matrix with high selectivity and efficiency. This approach is a promising method for selective extraction of PLs in lipidomics or phospholipidomics.