In conclusion, this study firstly indicated that XIST was increased in serum of patients with acute‐stage pneumonia and LPS‐injured WI‐38 cells; downregulation of XIST attenuated LPS‐induced apoptosis and inflammation in WI‐38 cells via modulating miR‐370‐3p/TLR4 axis. Here, TLR4 is linked to pneumonia.