Secreted protein acidic and rich in cysteine (SPARC) governs fundamental cellular functions such as cell adhesion, proliferation and differentiation, and also regulates the expression and activities of numerous growth factors and matrix metalloproteinases (MMPs) which are essential for degradation and turnover of extracellular matrix (ECM). In the lung,SPARC drives pathological responses in non-small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF) by promoting microvascular remodeling and excessive deposition of ECM proteins. However, the role of SPARC in chronic airway conditions, such as asthma and chronic obstructive pulmonary disease (COPD), has far been overlooked. This article reviewed current progress of its role in NSCLC and IPF, and highlighted its effect in chronic airway diseases such as asthma and COPD.