With the development of society, chronic obstructive pulmonary disease (COPD), a common respiratory disease, suffers an increasing incidence. To explore the correlation between high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), endothelin-1 (ET-1), and chronic obstructive pulmonary disease combined with pulmonary hypertension (COPD-PH), a total of 112 COPD patients admitted to our hospital from July 2017 to December 2020 were analyzed prospectively, of which 57 patients combined with PH were enrolled in the research group and the other 55 patients without PH were enrolled in the control group. Serum hs-CRP, IL-6, IL-10, ET-1, blood gas indexes, and related indexes of lung function of the two groups were detected and their correlations were analyzed. The research group was divided into the mild group, moderate group, and heavy group according to pulmonary average arterial pressure, and serum hs-CRP, IL-6, IL-10, ET-1, and disease severity were analyzed. Receiver operating characteristic curve (ROC) analysis was performed to serum hs-CRP, IL-6, IL-10, and ET-1 of COPD-PH patients, and independent risk factors for COPD-PH were analyzed. The research group showed significantly higher serum hs-CRP, IL-6, and ET-1 and significantly lower IL-10 expression than the control group (all P < 0.05); serum hs-CRP, IL-6, and ET-1 were negatively correlated with PaO2, FEV1, FVC, and FEV1/FVC and positively correlated with PaCO2; IL-10 was positively correlated with PaO2, FEV1, FVC, and FEV1/FVC and negatively correlated with PaCO2; hs-CRP, IL-6, and ET-1 were positively correlated with COPD-PH severity, and IL-10 was negatively correlated with it. hs-CRP, IL-6, IL-10, and ET-1 were closely and significantly related to the pathological process of COPD-PH, including onset and development, and the elevation of hs-CRP, IL-6, and ET-1 and decrease of IL-10 are independent risk factors for the onset of COPD-PH. With relatively high predictive value for COPD-PH, hs-CRP, IL-6, IL-10, and ET-1 can be promoted as predictors for it.