Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that is highly expressed in a variety of cancer tissues, promotes tumor cell proliferation and metastasis, and is involved in the tumor cell cycle and apoptosis. The aim of the present study was to assess the association between the expression of LRH-1 and the prognosis of patients with colon cancer. Immunohistochemistry was used to detect the expression of LRH1 in 128 cases of colon cancer and adjacent tissues. The 5-year survival rate was obtained from telephone follow-up data, outpatient review and through access to medical records. Positive expression of LRH-1 was found in 108/128 colon cancer samples, compared with 17/128 normal tissues. Statistical analysis showed that positive LRH-1 expression was significantly associated with clinical pathological stage, depth of invasion and lymph node metastasis. The overall survival (OS) rate of patients with positive LRH-1 expression was significantly lower than that of patients with low expression. Multivariate analysis showed that LRH-1 expression could be used as an independent predictor of OS. In conclusion, the present findings suggest that LRH-1 may serve an important role in the development and progression of colon cancer, with potential value as a prognostic molecular marker that could be used to assist in the diagnosis and evaluation of colon cancer. LRH-1 may become a target for novel therapies for patients with colon cancer.