The side effects of hydroxycamptothecin (HCPT) limit its clinical application in antitumor. The surface of hollow mesoporous polydopamine (HMPDA) was modified with the ANGPT2-specific peptide GSFIHSVPRH (GSF), followed by loading HCPT and indocyanine green (ICG) to form a drug-delivery system (ICG-GSF-HMPDA@HCPT). The morphology, particle size, HCPT loading capacity, and HCPT-release properties were characterized. The biocompatibility and antitumor efficacy of the delivery system were validated through in vitro and in vivo experiments. Micropositron emission tomography (PET)/computed tomography (CT) imaging showed that 68Ga-labeled GSF accumulated in the xenograft, and the targeting of GSF toward gastric cancer was confirmed. ICG-GSF-HMPDA@HCPT inhibited cell viability, colony formation, cell invasion, and migration of HGC-27 cells and showed a better suppression of xenograft development than HMPDA@HCPT. Furthermore, blood biochemical assays showed that ICG-GSF-HMPDA@HCPT exhibited favorable biosafety. Thus, the HCPT-loaded HMPDA modified with the ANGPT2-specific peptide was successfully constructed and served as a potent delivery for GC-targeted therapy.