Abstract: Objective To investigate the relationship between the onset time of neutropenia and the prognosis of patients with lung squamous cell carcinoma (LSCC) after non-surgical treatment. Methods A total of 290 LSCC patients after non-surgical treatment were enrolled and their clinical data were collected. The ROC curve was used to determine the optimal cutoff value for the occurrence time of neutropenia. According to the optimal cutoff value, the patients were divided into three groups: an early group (group A)and a late stage group (group B) and a non-appearance group (group C). The three groups were compared for their clinical characteristics and survival time, and their prognostic factors were analyzed by Cox regression univariate and multivariate analysis. Results The optimal cutoff value for the onset time of neutropenia was 36 days. The median survival time of patients in group A who received chemotherapy alone and concurrent chemoradiotherapy was 23 and 27 months, respectively, which was significantly higher than those in group B (16 and 20 months) and group C (11 and 17 months) (P<0.05). Multivariate Cox regression analysis showed that age, clinical stage, ECOG score, degree of differentiation, treatment methods, and NLR before treatment were the independent influencing factors for the overall survival of LSCC patients with non-surgical treatment. According to stratified analysis by treatment method, the onset time of neutropenia was related to the prognosis of patients in chemotherapy alone and concurrent chemoradiotherapy, and the risk of death in group B and group C was higher than that in group A (HR=1.816, P=0.017)(HR=3.198, P<0.05). Conclusions The onset time of neutropenia is an independent influencing factor for the prognosis of LSCC patients after chemotherapy alone and concurrent chemoradiotherapy. Monitoring the onset time of neutropenia is helpful to determine the early prognosis of LSCC patients who received chemotherapy alone or concurrent chemoradiotherapy and timely adjust chemotherapy dose to improve patient prognosis.