Over　the　past　two　decades,　gene　therapy,　as　a　promising　way　to　regulate　or　replace　abnormal　gene,　has　made　impressive　progress　with　numerous　clinic　trials.　However,　the　success　of　gene　therapy　was　hugely　limited　by　its　low　translocation　into　cytoplasm.　Therefore,　technologies　to　efficiently　protect　and　deliver　therapeutic　nucleic　acids　have　been　extensively　investigated,　but　most　of　the　delivery　strategies　involve　endosomal　entrapment,　leading　to　low　delivery　efficiency.　In　this　review,　we　discuss　the　latest　advances　in　nonendocytosis-dependent　strategies　for　delivering　nucleic　acids　into　cells.　A　highlight　is　provided　on　the　cellular　uptake　systems　facilitated　by　the　endosome-Golgi-endoplasmic　reticulum　pathway,　pH　low　insertion　peptides,　cell-penetrating　peptides,　scavenger　receptor-mediated　nonendocytosis,　membrane　fusion,　and　the　emerged　thiol-disulfide　exchange.　The　mechanisms,　pros,　and　cons　of　these　systems　are　discussed.　Finally,　current　challenges　and　future　perspectives　for　the　translation　of　nonendocytic　gene　delivery　vectors,　especially　thiol-mediated　cellular　uptake,　into　clinical　applications　are　discussed.　Copyright　©　2020　American　Chemical　Society.