Objective:To analyze the interaction of tissue delta-like ligand 3 (DLL3) expression and xeroderma pigmentosum gene G (XPG) gene polymorphism on the sensitivity of advanced lung squamous cell carcinoma to platinum-based chemotherapy.Methods:One hundred and forty patients with advanced squamous lung cancer admitted to Yuechi County People′s Hospital from March 2019 to December 2021 were selected and all were given carboplatin and paclitaxel for injection (albumin-bound) in a fully informed manner, with one cycle every 3 weeks for a total of 4 cycles of treatment. The patients were divided into sensitive group (46 cases) and non-sensitive group (94 cases) according to their sensitivity to chemotherapy. Baseline information, tissue DLL3 expression and XPG gene polymorphism were compared between the two groups, and tissue DLL3 expression in patients with different XPG genotypes was compared. Multi-factor Logistic regression analysis was used to analyzed the factors associated with the sensitivity to chemotherapy, and interaction coefficient γ was used to analyze tissue DLL3 expression and XPG.Results:The tissue DLL3 expression score of the sensitive group was lower than that in the non-sensitive group: (3.28 ± 0.93) scores vs. (7.59 ± 1.22) scores, there was statistical difference ( P<0.01). The patients with CC genotype in the sensitive group were more than those in the non-sensitive group, and the patients with CT and TT genotypes were less than those in the non-sensitive group ( P<0.05). Tissue DLL3 expression score in patients with CC, CT, TT genotype were (3.51 ± 0.93), (6.76 ± 1.08), (10.09 ± 1.12) scores, there was statistical difference ( P<0.05); and tissue DLL3 expression score was CC