Neonatal pneumonia is a high neonatal mortality disease. The current research was designed to elucidate the modulatory function and feasible molecular mechanism of UCA1 in LPS-induced injury in pneumonia. Herein, LPS was applied to induce WI-38 cell inflammatory damage. We displayed that UCA1 was elevated in LPSinjured WI-38 cells. In the functional aspect, intervention of UCA1 evidently aggrandized cell viability in LPS-triggered WI-38 cells. In the meanwhile, elimination of UCA1 distinctly assuaged cell apoptosis concomitant with declined levels of proapoptotic proteins Bax and C-caspase-3, and ascended the expression of antiapoptotic protein Bcl-2. Subsequently, disruption of UCA1 manifestly restrained inflammatory damage as characterized by declination of multiple pro-inflammatory factors IL-1β, IL-6, and TNF-α in WI-38 cells under LPS circumstance. More importantly, we predicted and verified that UCA1 functioned as a ceRNA by efficaciously binding to miR-499b-5p thereby inversely adjusting miR-499b-5p expression. Interesting, TLR4 was identified as direct target of miR-499b-5p, and positively regulated by UCA1 through sponging miR-499b-5p. Mechanistically, absence of miR-499b-5p or restoration of TLR4 impeded the beneficial effects of UCA1 ablation on LPSstimulated apoptosis and inflammatory response. Collectively, these observations illuminated that UCA1 inhibition protected WI-38 cells against LPS-managed inflammatory injury and apoptosis process via miR-499b-5p/TLR4 crosstalk, which ultimately influencing the development of pneumonia.