Yolk-shell-structured nanoparticles (YSNs) provide useful carriers for applications in biomedicine and catalysis due to the excellent loading capability and versatile functionality of the flexible core and porous shell. Unfortunately, the reported YSNs always require complex multistep synthesis processes and a harsh hard-template etching strategy. Herein, a facile "selective extraction" strategy is developed to synthesize yolk-shell-structured polymer@void@mSiO2 nanoparticles (designated as YSPNs) comprising deformable and soft polystyrene-b-poly(acrylic acid) (PS-b-PAA) micellar cores and mesoporous silica shells. The YSPNs are formed by a morphological change and volume shrinkage of the PS-b-PAA aggregates from large compound vesicles to large compound micelles during the extraction process. As a multidrug vehicle, both hydrophobic curcumin (Cur, 6.4 wt %) and hydrophilic doxorubicin hydrochloride (Dox, 19.4 wt %) can be coloaded onto YSPNs through a successive impregnation method. Moreover, the resulting Cur/Dox@YSPNs possess intelligent pH-responsive capability, time-sequenced release behavior, and high in vivo antitumor efficiency, demonstrating excellent potential as safe and efficient multidrug nanocarriers for tumor chemotherapy. We envision that such a facile "selective extraction" strategy will enable pathways to construct organic-inorganic hybrid nanoparticles with yolk-shell structures for various applications.