Objective To analyze the application value of serum heparin binding protein (HBP), the ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC), peak expiratory flow (PEF) in the evaluation of severity and prognosis of patients with chronic obstructive pulmonary disease (COPD), so as to provide reference for clinical treatment later stage. Methods A total of 60 cases patients with COPD who visited in the Zhangjiagang First People's Hospital from February 2019 to June 2021 were selected as the study group (with 25 cases in the stable period, the other 35 cases in the acute exacerbation period; with 47 cases in survival, the other 13 cases in death), another 60 cases healthy subjects who underwent physical examination at the same time were selected as the control group, a prospective research was carried. The levels of serum HBP, FEV1/FVC and PEF of research subjects between the control group and the study group, the levels of serum HBP, FEV1/FVC and PEF of patients in stable period and acute exacerbation period in the study group, the levels of serum HBP, FEV1/FVC and PEF of patients with different prognosis (survival and death) in the study group were compared; the correlation between serum HBP level and pulmonary function indexs of COPD patients were analyzed; the diagnostic value of HBP, FEV1/FVC and PEF for the prognosis of COPD patients were analyzed through drawing the receiver operator characterist (ROC) curve. Results The serum HBP level of patients in the study group was higher than that in the control group, and patients in acute exacerbation period were higher than that patients in the stable period, patients in death were higher than patients in survival; the levels of FEV1/FVC and PEF of patients in the study group were lower than those in the control group, and patients in the acute exacerbation period were lower than patients in the stable period, patients in death were lower than patients in survival (all P<0.05); the level of serum HBP was negatively correlated with the levels of FEV1/FVC and PEF in COPD patients (r =-0.652, -0.617, all P<0.05); the ROC curve results showed that, the area under the curve (AUC) of HBP, FEV1/FVC and PEF in predicting the prognosis of patientswere 0.855, 0.909 and 0.891, respectively, among them, the FEV1/FVC had the highest diagnostic value for the prognosis of COPD patients (all P<0.05). Conclusion Serum HBP, FEV1/FVC and PEF can reflect the condition and prognosis of COPD patients to a certain extent, and serum HBP is negatively correlated with FEV1/FVC and PEF respectively, among them FEV1/FVC has the highest diagnostic value for the prognosis of COPD patients, it has certain reference value for guiding clinical treatment and improving the prognosis of patients.