Objective　The　effects　of　zirconium　dioxide　nanoparticles　(ZrO2-NPs)　exposure　on　the　histone　H3　modification　in　human　skin　keratinocytes　(HaCaT)　were　clarified,　and　the　underlying　mechanism　of　histone　H3　modification　changes　was　explored　in　this　study　to　provide　a　theoretical　basis　for　the　further　safe　application　of　nanomaterials.　Methods　The　ZrO2-NPs　were　firstly　characterized　in　detail　by　means　of　scanning　electron　microscope,　laser　particle　size　analyzer,　X-rad　diffraction,　etc.　Subsequently,　the　effects　of　ZrO2-NPs　exposure　on　the　cell　viability,　intracellular　accumulation　and　histone　H3　modification　were　evaluated　by　Western　blotting　and　flow　cytometry.　Results　The　results　showed　that　ZrO2-NPs　after　dispersion　treatment　exhibited　obvious　agglomeration,　and　their　specific　surface　area　decreased　whereas　the　secondary　particle　size　increased.　The　phosphorylation　of　histone　H3　at　serine　10,　the　acetylation　of　histone　H3　at　lysine　9　and　14,　the　trimethylation　of　histone　H3　at　lysine　4　and　27　were　induced　to　upregulate　by　ZrO2-NPs　in　a　short　time　(1　h).　Through　further　analysis,　it　was　found　that　the　intracellular　accumulation　of　ZrO2-NPs　and　the　level　of　DNA　damage　caused　by　ZrO2-NPs　were　linearly　correlated　with　the　level　of　histone　H3　modification　induced　by　ZrO2-NPs.　Conclusion　These　results　suggested　that　the　changes　of　the　common　modification　sites　of　histone　H3　in　HaCaT　cells　were　induced　after　exposure　of　ZrO2-NPs.　The　intracellular　accumulation　of　ZrO2-NPs　is　one　of　the　key　factors　in　its　induction　of　changes　in　histone　H3　modification,　and　regulation　mechanism　of　histone　H3　modification　may　be　involved　in　DNA　damage　repair　pathways.