DNA　structural　nanotechnology　is　of　significant　importance　for　the　understanding,　diagnosis　and　treatment　of　human　diseases.　However,　few　reports　have　examined　whether　DNA　structural　nanotechnology　can　be　suitable　for　predicting　the　malignant　invasion　of　tumor　cells　and　preventing　cancers.　It　is　mainly　because　complex　design　of　numerous　DNA　building　blocks　and　susceptibility　of　nanostructures,　including　DNA　hydrogels,　to　nuclease　degradation　as　critical　issues　hamper　the　transition　to　clinical　application.　Moreover,　intracellular　assembly　of　DNA　nanostructures　in　a　very　simple　manner　is　unexplored　because　of　technical　limitations.　In　current　study,　by　palindromic　end-mediated　cross-linking　hybridization　chain　reaction　(c-HCR),　we　report　intracellular　invasive　growth　of　DNA　hydrogel　network　(2　h-DNH)　from　only　two　hairpins　in　a　sequential　manner,　where　the　palindromic　fragment　in　DNA　building　blocks　substantially　simplifies　the　probe　design　and　assembly　process.　Macroscopic　2　h-DNH　can　be　visualized　by　naked　eye　and　remain　its　structural　integrity　over　12-h　incubation　in　intracellular　environment.　The　c-HCR　strategy　can　be　used　to　screen　intracellular　miRNAs　with　the　detection　sensitivity　improved　by　almost　2　~　3　orders　of　magnitude.　Diseased　cells　(HeLa)　are　discriminated　from　healthy　cells　(HEK-293),　and　MCF-7　cells　with　different　levels　of　miR-21　are　accurately　identified.　Even　without　clinical　symptoms,　the　invasion　of　malignant　tumor　cells　is　predicted　by　visualizing　intracellular　2　h-DNH.　Moreover,　c-HCR-guided　therapeutic　intervention　can　hamper　the　tumorigenesis,　indicating　the　great　potential　application　in　the　early　warning　and　prevention　of　human　cancers.　©　2021　Elsevier　B.V.