Myocardial infarction (MI) is a severe disease that could lead to reversible or irreversible ischemic heart damage. A previous study has revealed that microRNA mmu-miR-210-3p expression is downregulated in fat-1 transgenic mice post-MI. Nevertheless, the specific mechanism of miR-210-3p in MI remains obscure. In this study, we observed that miR-210-3p expression was downregulated in the mice's left ventricle post-MI, and miR-210-3p expression was suppressed while cell apoptosis was promoted in H9c2 cells under hypoxia condition. Besides, miR-210-3p overexpression could enhance cell proliferation and inhibit cell apoptosis in hypoxia-treated H9c2 cells. Then, molecular mechanism assays revealed that miR-210-3p overexpression could activate the PI3K/Akt pathway, and nuclear factor of kappa light polypeptide gene enhancer in B cells 1 (Nfkb1) was the target of miR-210-3p. In addition, RNA imprinted and accumulated in nucleus (Rian), a long noncoding RNA, could sponge miR-210-3p to upregulate Nfkb1 expression. Besides, Nfkb1 was verified to facilitate the transcription of Rian by binding with a Rian promoter. Furthermore, rescue assays revealed that both Nfkb1 and PI3K/Akt pathway are engaged in the Rian-mediated cell proliferation and apoptosis in hypoxia-treated H9c2 cells. In conclusion, a Rian/miR-210-3p/Nfkb1 feedback loop enhances hypoxia-induced cell apoptosis in MI through deactivating the PI3K/Akt pathway.