The　rapid　development　of　CRISPR/Cas9　systems　has　opened　up　tantalizing　prospects　to　sensitize　cancers　to　chemotherapy　using　efficient　targeted　genome　editing,　but　safety　concerns　and　possible　off-target　effects　of　viral　vectors　remain　a　major　obstacle　for　clinical　application.　Thus,　the　construction　of　novel　nonviral　tumor-targeting　nanodelivery　systems　has　great　potential　for　the　safe　application　of　CRISPR/Cas9　systems　for　gene-chemo-combination　therapy.　Here,　we　report　a　polyamidoamine-aptamer-coated　hollow　mesoporous　silica　nanoparticle　for　the　co-delivery　of　sorafenib　and　CRISPR/Cas9.　The　core-shell　nanoparticles　had　good　stability,　enabled　ultrahigh　drug　loading,　targeted　delivery,　and　controlled-release　of　the　gene-drug　combination.　The　nanocomplex　showed　＞60%　EGFR-editing　efficiency　without　off-target　effects　in　all　nine　similar　sites,　regulating　the　EGFR-PI3K-Akt　pathway　to　inhibit　angiogenesis,　and　exhibited　a　synergistic　effect　on　cell　proliferation.　Importantly,　the　co-　delivery　nanosystem　achieved　efficient　EGFR　gene　therapy　and　caused　85%　tumor　inhibition　in　a　mouse　model.　Furthermore,　the　nanocomplex　showed　high　accumulation　at　the　tumor　site　in　vivo　and　exhibited　good　safety　with　no　damage　to　major　organs.　Due　to　these　properties,　the　nanocomplex　provides　a　versatile　delivery　approach　for　efficient　co-loading　of　gene-drug　combinations,　allowing　for　precise　gene　editing　and　synergistic　inhibition　of　tumor　growth　without　apparent　side　effects　on　normal　tissues.