Objective 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 HTR-8/ Svneo trophoblast cells were cultured in vitro and separated into control, interference empty (transfected with small interfering RNA-normal control (si-NC)), si-XIST-1 (transfected with si-XIST-1), si-XIST-1+anti-NC (co-transfected with si-XIST-1 and anti-NC), and si-XIST-1+anti-182-5p (co-transfected with si-XIST-1 and anti-182-5p) groups. XIST, miR-182-5p, and hypoxia inducible factor-2α (HIF-2α) mRNA expression levels were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2’-deoxyuridine (EdU) assays. Apoptosis was detected by flow cytometry. Cell migration and invasion abilities were measured by scratch-healing and Transwell experiments. HIF-2α, cleaved-caspase-3, Bcl-2, Bax, matrix metalloproteinase (MMP)-2, and MMP-9 protein levels in cells were measured by Western blot. The targeting relationship of miR-182-5p with XIST and HIF-2α was verified by dualluciferase reporter assay. Results XIST and HIF-2α mRNA levels, apoptosis rate, and HIF-2α, cleaved-caspase-3,and Bax protein levels in the si-XIST-1 group were lower than those in the control and interference empty groups,while miR-182-5p, cell viability, EdU-positive rate, scratch-healing rate, number of invaded cells, and Bcl-2, MMP-2, and MMP-9 protein levels were higher (P<0. 05). HIF-2α mRNA level, apoptosis rate, and HIF-2α, cleavedcaspase-3, and Bax protein levels in the si-XIST-1+anti-182-5p group were higher than those in the si-XIST-1 and siXIST-1+ anti-NC groups, while miR-182-5p, cell viability, EdU-positive rate, scratch-healing rate, number of invaded cells, and Bcl-2, MMP-2, and MMP-9 protein levels were lower (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. Conclusions 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.