Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/β-catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/β-catenin signaling pathway. However, the expression pattern and clinicopathological significance of SOX7 in patients with lung adenocarcinoma is still unclear. To address this problem, the SOX7 mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemical studies were performed on 288 pairs of adjacent normal lung and lung adenocarcinoma tissues with complete follow-up records. Association of SOX7 protein expression with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. SOX7 mRNA expression was significantly down-regulated in lung adenocarcinoma compared with matched adjacent normal tissues (P < 0.001). SOX7 protein was expressed in the cytoplasm of lung adenocarcinoma cells in 106/288 (36.8 %) of cases, whereas its immunoreactivities were predominantly located in the cytoplasm of the adjacent normal tissues. The reduced SOX7 expression was correlated with poor differentiation (P = 0.002), lymph node metastasis (P = 0.011) and advanced TNM stage (P = 0.006). Regarding patient survival, the overall survival and the disease-free survival rates were both significantly lower in patients with SOX7-negative tumors than in those with SOX7-positive tumors (P = 0.018 and 0.013, respectively). Multivariate analysis using a Cox proportional-hazards model demonstrated that SOX7 expression status was an independent prognostic factor predicting the overall survival and the disease-free survival of patients with lung adenocarcinoma (P = 0.021 and 0.016, respectively).Our data suggest that the decreased expression of SOX7 is an important feature of lung adenocarcinoma. The expression level of SOX protein may be a useful prognostic marker for patients with lung adenocarcinoma.