Objective: MicroRNAs (miRNAs) have been found to play important roles in the development of non-small cell lung carcinoma (NSCLC). The aim of this study was to analyze the expression and clinical value of serum miR-185 in NSCLC. Methods: Serum miR-185 levels were detected in 146 NSCLC patients, 50 patients with carcinoma in situ, 25 patients with non-malignant lung diseases (NMLD), and 80 healthy controls using quantitative reverse transcription PCR. The correlation between serum miR-185 level and clinical status of NSCLC was explored. Results: The results revealed that serum miR-185 expression was progressively decreased in healthy controls, patients with NMLD, patients with carcinoma in situ and NSCLC patients. In addition, compared to carcinoembryonic antigen (CEA), serum miR-185 demonstrated better diagnostic accuracy for discriminating patients with carcinoma from healthy controls, NSCLC patients from healthy controls and NSCLC patients from patients with carcinoma in situ. In addition, serum miR-185 levels were significantly elevated in post-treated samples compared to the pre-treated samples. Moreover, reduced serum miR-185 was closely associated with unfavorable clinicopathological parameters and worse survival. Univariate and multivariate cox regression analysis confirmed that serum miR-185 was an independent prognostic indicator for NSCLC. Conclusions: Collectively, our findings have demonstrated that serum miR-185 might serve as a promising and robust biomarker for the early detection and prognosis prediction of NSCLC.