Objective To analyze the expression of serum miR-21 and miR-155 in patients with chronic obstructive pulmonary disease (COPD) and their relationship with pulmonary hypertension (PH). Methods One hundred and twenty patients with COPD treated in Nanyang Central Hospital from March 2019 to March 2021 were selected as the research subjects. After admission, the occurrence of PH in patients was evaluated by cardiac color Doppler ultrasound, and the patients were divided into occurrence group and nonoccurrence group. The levels of serum miR-21 and miR-155 were detected at admission, and the relationship between the levels of serum miR-21, miR-155 and PH in patients with COPD was analyzed. Results PH occurred in 26 cases, accounting for 21.67% of the 120 patients with COPD. There was no statistical significant difference in gender, age and pulmonary function classification between the two groups (P>0.05). The levels of serum miR-21 and miR-155 in the occurrence group were higher than those in the nonoccurrence group (P<0.05). The results of Logistic regression analysis showed that the overexpression of serum miR-21 and miR-155 was related to the occurrence of pH in patients with COPD (P<0.05). Conclusion The overexpression of serum miR-21 and miR-155 has a certain relationship with PH in patients with COPD.