Significance Long noncoding RNAs (lncRNAs) are important regulators of gene expression, but their structural features are largely unknown. We used structure-selective chemical probing to examine the structure of the Xist lncRNA in living cells and found that the RNA adopts well-defined and complex structures throughout its entire 18-kb length. By looking for changes in reactivity induced by the cellular environment, we were able to identify numerous previously unknown hubs of protein interaction. We also found that the Xist structure governs specific protein interactions in multiple distinct ways. Our results provide a detailed structural context for Xist function and lay a foundation for understanding structure–function relationships in all lncRNAs.