Endometrial　cancer　(EC)　is　a　malignancy　that　severely　threatens　women＇s　health　and　there　is　an　urgent　need　to　find　novel　natural　compounds　as　effective　treatment　drugs.　At　the　same　time,　multi-omics　analysis　of　cells　has　been　widely　used　in　basic　research　to　find　new　pathogenesis　and　mechanisms.　Due　to　the　lack　of　data　on　the　functional　importance　of　mRNAs　and　miRNAs　in　plant-derived　asparanin　A　(AA)　induced　cancer　cells,　the　underlying　mechanisms　of　AA　on　endometrial　cancer　(EC)　Ishikawa　cells　were　investigated　using　mRNA-seq　and　miRNA-seq,　qRT-PCR,　western　blot,　and　immunohistochemistry.　The　combined　analysis　of　37　differentially　expressed　miRNAs　(DEMs)　and　489　differentially　expressed　genes　(DEGs)　with　negative　regulatory　relationships　revealed　that　AA　not　only　induced　apoptosis,　but　also　triggered　autophagy　through　endoplasmic　reticulum　(ER)　stress　and　DNA　damage-related　pathways.　23　DEMs　and　39　DEGs　participated　in　protein　processing　in　the　endoplasmic　reticulum　(PPER)　and　p53　signaling　pathways,　as　shown　by　miRNA-target　gene　network　analyses.　Among　them,　we　concluded　that　miR-6236-p5,　miR-1246-p5,　miR-11987_L-1,　PC-5p-21544,　and　miR-5100-p3_1ss17TC　function　as　hub　miRNAs,　and　their　regulation　may　be　essential　for　the　anti-cancer　activity　of　AA.　This　study　may　provide　a　comprehensive　understanding　of　the　potential　anticancer　regulation　of　AA　on　EC,　suggesting　AA　as　a　potential　candidate　for　dietary　supplementation　in　cancer　medication　and　prevention.　©　The　Royal　Society　of　Chemistry　2020.