Aim: To investigate the molecular mechanism by which long chain non coding RNA (lncRNA) X inactive specific transcript (XIST) regulates the biological activity of trophoblast cells. Methods: Human trophoblast cells HTR-8/Svneo were cultured in vitro and separated into control group, interference empty group (transfected with si-NC), si-XIST-1 group (transfected with si-XIST-1), si-XIST-1+anti-NC group (co transfected with si-XIST-1 and anti-NC), si-XIST-1+anti-182-5p group (co transfected with si-XIST-1 and anti-182-5p). Real-time fluorescence quantitative PCR (qRT-PCR) was applied to measure the expression of XIST, miR-182-5p, and hypoxia inducible factor-2α (HIF-2α) mRNA in cells. CCK-8 experiment and EdU experiment were applied to detect cell proliferation activity. Flow cytometry was applied to detect cell apoptosis. Scratch healing experiment and Transwell experiment were applied to measure cell migration and invasion abilities. Western blot was applied to measure the expression of HIF-2a, cleared-caspase-3, Bcl-2, Bax, matrix metalloprotein (MMP)-2, and MMP-9 proteins in cells. Dual luciferase reporter assay was applied to verify the targeting relationship of miR-182-5p with XIST and HIF-2α. Results: Compared with control group and interference empty group, mRNA levels of XIST and HIF-2α, apoptosis rate, protein levels of HIF-2α, cleaved caspase-3, and Bax were decreased in si-XIST-1 group; the level of miR-182-5p, cell viability, EdU positive rate, scratch healing rate, number of invaded cells and the protein levels of Bcl-2, MMP-2 and MMP-9 were increased (P<0.05). Compared with si-XIST-1 group and si-XIST-1+anti-NC group, mRNA level of HIF-2α, apoptosis rate, protein levels of HIF-2α, cleaved caspase-3, and Bax were increased in si-XIST-1+anti-182-5p group; the level of miR-182-5p, cell viability, EdU positive rate, scratch healing rate, number of invaded cells and the protein levels of Bcl-2, MMP-2 and MMP-9 were decreased (P<0.05). LncRNA XIST was able to target miR-182-5p in HTR-8/Svneo cells, and HIF-2α was the target of miR-182-5p. Conclusion: Knocking-down lncRNA XIST may inhibit HIF-2α expression by competitively binding to miR-182-5p, thereby enhancing the proliferation, migration, and invasion abilities of HTR-8/Svneo cells, and inhibiting cell apoptosis.