To explore the effect of Senecio scandens ethanol extract on Streptococcus pneumoniae-evoked alveolar epithelial cell damage and its molecular mechanism. Alveolar epithelial cells and Streptococcus pneumonia infected alveolar epithelial cells were incubated with Senecio scandens ethanol extract. Western blotting measured cleaved caspase-3 protein expression. Quantitative reverse transcription-polymerase chain reaction detected SNHG16 and microRNA-542-3p levels, and the dual-luciferase reporter assay investigated the targeting relationship between them. After treatment with different concentrations of Senecio scandens ethanol extract, alveolar epithelial cell survival rate did not change, while the survival rate of alveolar epithelial cells infected by Streptococcus pneumoniae was gradually decreased, and the decrease was stable at 32 μg/ml. After treatment with 8, 16, 32 μg/ml Senecio scandens ethanol extract, the apoptotic rate and inflammation of alveolar epithelial cells infected by Streptococcus pneumoniae, inflammation was repressed. Senecio scandens ethanol extract dose-dependently reduced SNHG16, but elevated microRNA-542-3p in cells. After SNHG16 knockdown, microRNA-542-3p levels were boosted, apoptotic rate was declined, and inflammation was inhibited (p<0.05). Overexpression of SNHG16 could reverse the effects of Senecio scandens ethanol extract on the apoptosis and inflammatory factors of alveolar epithelial cells infected by Streptococcus pneumoniae. SNHG16 targeted microRNA-542-3p. Senecio scandens ethanol extract could impair Streptococcus pneumoniae-evoked alveolar epithelial cell injuries by regulating the SNHG16/microRNA-542-3p axis.