Background Posterior capsule opacification (PCO), also known as after-cataract, is a special condition in which the cortex of the cataract remains in the pupil area or the formation of a fibrogenic membrane after surgical cataract extraction. Objective To explore the effect of lncRNA X inactivation-specific transcript (XIST) on PCO. Results First, we proved that XIST was up-regulated in TGF-β2-treated SRA01/04 cells. Inhibition of XIST significantly reduced the proliferation and migration of SRA01/04 cells, and affected the expression of EMT markers. Further research data illustrated that miR-98-5p and COL5A2 were targets of XIST. Besides, pathway enrichment analysis showed that the PI3K/Akt/FOXO1 signaling pathway was associated with XIST. Conclusion In the study, we demonstrated that lncRNA XIST contributed to EMT in PCO via regulating miR-98-5p/COL5A2 and PI3K/Akt/FOXO1 pathway, which provided a new treatment strategy for PCO.