Background:　Nanotopography　directs　stem　cell　fate;　however,　the　underlying　mechanisms,　especially　those　at　the　epigenetic　level,　remain　vague.　The　TiO2-nanotube　array,　a　classical　example　of　nanotopography,　is　a　good　model　to　investigate　topography-cell　interactions　because　of　its　good　controllability　and　easy　manufacturing　process.　Previously,　we　found　that　a　TiO2-nanotube　array　with　an　optimal　diameter　promoted　osteogenic　differentiation　of　human　adipose-tissue-derived　stem　cells　(hASCs).　Methods:　We　used　RNA　sequencing　and　bioinformatics　to　reveal　the　overall　gene　expression　profile　of　hASCs　on　TiO2-nanotube　arrays.　Results:　Bioinformatics　analyses　revealed　that　the　epigenetic　regulatory　network　plays　an　important　role　in　TiO2-nanotube-guided　osteogenic　differentiation.　Changes　in　cell　adhesion　and　cytoskeletal　reorganization　are　linked　to　epigenetic　alterations,　including　upregulation　of　KDM4E　and　downregulation　of　histone　deacetylases.　Meanwhile,　microRNAs,　including　miR-24-1-5p,　miR-24-3　p,　miR-154-3　p,　miR-154-5　p,　miR-433-5　p,　miR-589-3　p,　and　miR-589-5　p　were　downregulated,　whereas　miR-186-5　p　and　miR-770-5　p　were　upregulated.　Long　non-coding　RNAs,　including　LINC00941,　LINC01279,　and　ZFAS1,　were　downregulated　in　this　process.　Conclusion:　Using　next-generation　sequencing,　we　illustrated　the　overall　picture　of　the　regulatory　mechanisms　of　TiO2　nanotubes,　thus　providing　a　basis　for　future　clinical　applications　of　nanotopography　in　the　field　of　bone　tissue　engineering.　Our　results　offer　insights　into　materialbased　nanomedicine　and　epigenetic　therapy.