Chronic kidney disease (CKD) is a persistent kidney structural and functional disorder. Quercetin is one of active extracted flavonoids and has protective effects. Therefore, we proposed to survey the effect of Quercetin on CKD. HK‐2 cells were preprocessed by Quercetin and then irritated with lipopolysaccharide (LPS). CCK‐8 assay and flow cytometry were utilized to test viability and apoptosis. ELISA assay was utilized to estimate the IL‐6 and TNF‐α secretion. Western blot was performed to examine the expression of apoptosis and inflammation‐associated mediators. After that HK‐2 cells were transfected by miR‐124 inhibitor. And the above‐mentioned parameters were reassessed. LPS stimulated apoptosis and declined viability in HK‐2 cells. Additionally, LPS stimulated inflammatory responses. Meanwhile, Quercetin attenuated LPS‐stimulated apoptosis, production of IL‐6, and TNF‐α in experimental cells. Subsequently, MyD88 and miR‐124 expression was elevated by LPS and alleviated by Quercetin. Finally, Quercetin exerted its protective function through NF‐κB pathway via up‐regulating miR‐124. Our data demonstrated that Quercetin reduced apoptosis and inflammation stimulated by LPS in HK‐2 cells. Moreover, Quercetin alleviated LPS‐stimulated injury by up‐regulating miR‐124.