BackgroundThe histone lysine‐specific demethylase (LSD1) is a key chromatin modifier mediating the demethylation of both H3K4me1/me2 and H3K9 me1/me2. Recently, its deregulation has been implicated in the initiation and progression of various cancers. The aim of this study was to investigate the expression pattern of LSD1 in tongue squamous cell carcinoma (SCC) and determine its prognostic significance in predicting patients' prognosis.MethodsLSD1 expression was examined by RT‐PCR and western blotting in three tongue cancer cell lines and by immunohistochemistry in 63 primary tongue SCC specimens with detailed clinical, pathological, and follow‐up data. Its associations with various clinicopathological parameters, Ki‐67 expression, and patients' survival were further assessed.ResultsUpregulated LSD1 expression was observed in tongue cancer cells and a major fraction of tongue SCC samples. Overexpression of LSD1 significantly associated with tumor size (P = 0.0357), pathological grade (P = 0.0323), Ki‐67 abundance (P = 0.0148), and reduced overall and disease‐free survival (Kaplan–Meier analysis, P = 0.0351, 0.0479, respectively). The Cox regression survival analyses identified LSD1 as an important independent predictor for patients' overall survival.ConclusionOur data indicate that aberrant LSD1 overexpression associates with key clinicopathological features and unfavorable prognosis in patients with tongue cancer. LSD1 might play critical roles during tongue tumorigenesis and represent a novel biomarker and potential therapeutic target for this malignancy.