To identify factors associated with the severity of chemotherapy-induced nausea and vomiting (CINV) in patients with lung squamous cell carcinoma.A retrospective analysis was conducted on 301 LSCC patients who received chemotherapy between January 2021 and December 2024. CINV severity was assessed using the Index of Nausea, Vomiting, and Retching. Post-chemotherapy assessments included blood measurements, inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and serum albumin levels. Multivariate logistic regression was performed to identify factors associated with CINV severity.A history of coronary heart disease significantly increased the risk of moderate to severe CINV (P = 0.010). Higher forced expiratory volume in one second (FEV1) was associated with a reduced risk of severe CINV (P = 0.053). Higher albumin levels were associated with more severe CINV (P = 0.048). Elevated IL-6 levels were found to have a protective effect against severe CINV (P < 0.001). Higher partial pressure of oxygen (PaO2) significantly reduced the risk of severe CINV (P = 0.002), while increased partial pressure of carbon dioxide (PaCO2) was associated with greater CINV severity (P = 0.017).CINV severity in LSCC patients is influenced by a combination of pulmonary function (FEV1, PaO2, PaCO2), inflammatory markers (IL-6, CRP, TNF-α), serum albumin levels, and cardiovascular comorbidities. These findings provide a foundation for personalized supportive care to enhance the quality of life in patients receiving chemotherapy.AJTR Copyright © 2025.