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Zheng He,1,2,* Lianhua Yu,3,* Shiyi Luo,4 Qi Li,5 Shuhong Huang,6 Yunhe An1 1Biotechnology Department, Beijing Center for Physical and Chemical Analysis, Beijing 100094, People’s Republic of China; 2Department of Clinical Laboratory, Chinese People’s Liberation Army General Hospital, Beijing 100853, People’s Republic of China; 3Department of Laboratory Medicine, Taizhou Municipal Hospital, Taizhou 318000, People’s Republic of China; 4State Key Laboratory of Physical Chemistry of Solid Surfaces and Department of Chemistry College and Chemical Engineering, Xiamen University, Xiamen 361005, People’s Republic of China; 5Department of Clinical Laboratory, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, People’s Republic of China; 6Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong 250062, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yunhe AnDepartment of Biotechnology, Beijing Center for Physical and Chemical Analysis, No. 7 Fengxian Middle Road, Beijing 100094, People’s Republic of ChinaTel +86-10-58717639Fax +86-10-58717638Email anyunhe_bio@163.comPurpose: Regulator of G-protein signaling (RGS) proteins are GTPase-activating proteins that target the α-subunit of heterotrimeric G proteins. Many studies have shown that RGS proteins contribute to tumorigenesis and metastasis. However, the mechanism in which RGS proteins, especially RGS4, affect the development of non-small cell lung cancer (NSCLC) remains unclear. The aim of this study was to characterize the role of RGS4 in NSCLC.Methods: RGS4 expression in NSCLC tissues was assessed using an immunohistochemistry tissue microarray. Additionally, RGS4 was knocked down using short-hairpin RNA to assess the regulatory function of RGS4 in the biological behaviors of human NSCLC cell lines. A