Background and objective Isoliquiritigenin(ISL)is an important pharmacological constituent of Glycyrrhiza glabra,which possesses a range of physiological and pharmacological activities,as well as significant antitumor ac-tivity,and can be used as a potential drug for targeted cancer therapy.LINC01503 is an oncogene,which has been closely asso-ciated with the malignant biological processes of many cancers.The aim of this study was to investigate the effects of ISL on the proliferation,apoptosis,invasion and migration oflung squamous carcinoma cells by regulating LINC01503.Methods Plasma was collected from lung squamous carcinoma patients and healthy individuals treated at Tangshan People's Hospital from Janu-ary 2021 to December 2022.The expression of LINC01503 in lung squamous carcinoma plasma,tissues and cells was detected by real-time quantitative fluorescence polymerase chain reaction(qRT-PCR).Lung squamous carcinoma cells were treated with different concentrations of ISL for 24 h,and LINC01503 expression was detected by qRT-PCR.The cells were treated in groups:si-NC group,si-LINC01503 group,DMSO(0.1％dimethyl sulfone)group,ISL group,pc DNA3.1(+)-NC group,pc DNA3.1(+)-LINC01503 group,ISL+pc DNA3.1(+)-NC group and ISL+pc DNA3.1(+)-LINC01503 groups.CCK-8 assay,clone formation assay,flow cytometry,Transwell assay and scratch assay were used to explore the effect of LINC01503 on the functional phenotype of lung squamous carcinoma cells.Results Fluorescence in situ hybridization results showed that the average fluorescence intensity of LINC01503 in tissue microarrays of lung squamous carcinoma patients was higher than that in paracancerous tissues(P＜0.05).The expression of LINC01503 in the plasma of patients with lung squamous carcinoma was higher than that in the plasma of healthy individuals(P＜0.05).Knockdown of LINC01503 inhibited the proliferation,invasion and migration of lung squamous carcinoma cells and promoted apoptosis(P＜0.05).ISL inhibited the proliferation,invasion,migration and promoted apoptosis of lung squamous carcinoma cells(P＜0.05).Overexpression of LINC01503 followed by intervention with ISL reversed the promotional effect of overexpression of LINC01503 on the proliferation,invasion and migration of lung squamous carcinoma cells as well as the inhibitory effect on apoptosis(P＜0.05).Conclusion LINC01503 was highly expressed in lung squamous carcinoma,and LINC01503 could promote the proliferation,invasion and migra-tion of lung squamous carcinoma cells and inhibit the apoptosis,ISL could inhibit the proliferation,invasion and migration of lung squamous carcinoma cells and promote apoptosis of lung squamous carcinoma cells by regulating the expression of LINC01503.