〔Abstract〕 Objective To investigate the effect of interleukin-1β(IL-1β) on lung squamous cell proliferation and its mechanism. Methods CBA kit was used to detect the content of IL-1β in plasma of patients with lung squamous cell carcinoma(n=20) and healthy controls(n=20). The effect of IL-1β on lung squamous cell proliferation was evaluated by plate cloning formation experiment. The effect of IL-1β on the expression of miR-223-3 p in SK-MES-1 cells was detected by qRT-PCR. The potential downstream target genes of miR-223-3 p were verified by TargetScan software, double lucigenase reporting experiment and Western blot. CCK-8 assay was used to detect the effect of down-regulated p27 kip1 on cell proliferation. Confocal microscope was used to observe the distribution of p27 kip1 in SK-MES-1. Western blot was used to analyze the effect of IL-1β on the expression of p27 kip1 in SK-MES-1 cells. Results The median IL-1β content in plasma of patients with lung squamous cell carcinoma was 11.96(7.55, 29.20)ng/L, which was higher than the healthy control group by 2.52(1.64, 3.48)ng/L, and the difference was statistically significant(Z=-5.06,P<0.001). IL-1β can promote the cloning formation of SK-MES-1 cells in lung squamous cell carcinoma and significantly reduce the expression of miR-223-3 p in cells. miR-223-3 p directly binded to the 3′UTR of CDKN1 B(p27 kip1) and inhibited its expression. After p27 kip1 was down-regulated, SK-MES-1 cell proliferation ability was significantly reduced. p27 kip1 was mainly distributed in the cytoplasm of SK-MES-1 cells, and IL-1β can promote the expression of p27 kip1. Conclusion IL-1β promotes cell proliferation by regulating the expression of miR-223-3 p and p27 kip1 in lung squamous cell carcinoma cells.