Polymorphisms located at microRNA (miRNA) binding sites may interfere with the miRNA/mRNA interaction. The objective of this study was to identify the association between a single nucleotide polymorphism (774 T> C) in 3'-untranslated region (3'-UTR) of Epithelial Growth Factor Receptor (EGFR) and development of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD) as well as to explore the molecular mechanism. In this study, we validated EGFR as a target of miR-214 in pulmonary artery smooth muscle cell (PASMC), which was further confirmed by the observation that exogenous overexpression of miR-214 significantly downregulated the expression of EGFR in the PASMCs genotyped as TT or TC, but not in CC group. Meanwhile, we found COPD patients with CC genotype had significantly higher risk for PH (OR= 1.965, p= 0.0095), compared with TT and TC genotypes,. Additionally, the PASMCs were isolated from 72 COPD patients, with which miR-214 and EGFR expression levels were determined, and we found that miR-214 level was comparable between each genotype group, the concentration of EGFR in CC genotype group was significantly higher than in TT or TC genotype group. Our study confirmed that EGFR 3'UTR 774 T> C polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of PH in COPD.