Feasible design is essential to achieve ideal chemical and biological properties of nanomaterials. For the first time, new nanocomposites with a polydopamine coating on hierarchically ordered macro-/mesoporous silica functionalized with titanium ions (denoted as HOMMS-PD-Ti4+) were prepared through a facile reaction route at room temperature. The applicability of as-synthesized HOMMS-PD-Ti4+ for the selective enrichment of phosphopeptides was tested. The experimental results demonstrate that, by taking advantage of the pure phosphate–Ti4+ interface and high loading amount of Ti4+, HOMMS-PD-Ti4+ presents remarkable selectivity for phosphopeptides, even at a low molar ratio of phosphopeptides/non-phosphopeptides (1:1000) with a very rapid enrichment speed (within 1 min). The superior sensitivity for low-abundant phosphopeptides and the high selectivity and effectiveness for the enrichment of phosphopeptides from human serum are also proven. These outstanding features demonstrate that HOMMS-PD-Ti4+ exhibits great potential in phosphoproteome research in the future.