BackgroundLRH1, which promotes the malignant transformation of carcinoma, has recently been documented in several types of malignancies. However, LRH1 has not been assessed as a potential clinical biomarker in any cancer.MethodsLRH1 expression was tested in fresh‐frozen tissue samples with quantitative real‐time PCR and Western blot analysis. Surgically resected tumor tissues were collected from 156 non‐small cell lung cancer (NSCLC) patients: 75 with adenocarcinoma and 81 with squamous cell carcinoma. Subsequently, the immunohistochemical expression of LRH1 was examined, and its clinical significance was evaluated.ResultsLRH1 overexpression was observed in NSCLC carcinoma tissues compared to adjacent normal lung tissues. LRH1 expression was correlated with poorer differentiation (P = 0.023), pathological tumor classification (P < 0.001), advanced pathological tumor node metastasis stage (P = 0.017), adenocarcinoma subtype (P = 0.031), and positive lymph node metastasis (P < 0.001). Multivariate analysis demonstrated that LRH1 expression status was an independent prognostic factor for overall (hazard ratio 1.372, 95% confidence interval 1.225–1.617; P = 0.003) and disease‐free survival (hazard ratio 1.497, 95% confidence interval 1.059–2.115; P = 0.011) in patients who suffered from resectable NSCLC.ConclusionThe results of our study indicate that LRH1 predicts NSCLC progression, metastasis, and a dismal prognosis, emphasizing its promising role as a novel target in NSCLC therapies.