The signal transducers and activators of transcription 3 (Stat3) has been detected in many types of cancer and plays an important role in tumour‐cell survival, proliferation, self‐renewal and invasion. To address the possibility that Stat3 may be involved in the metastasis and prognosis in lingual squamous cell carcinoma, we examined whether Stat3 expression associates with metastasis or survival rate in human clinical samples. We found that there was a significant correlation between Stat3 expression and lymph node metastasis (P = 0.009), stages (P = 0.029), recurrence (P = 0.0032) and death (P = 0.0356). The specific knockdown of Stat3 by RNA interference strongly inhibited the motile and invasion activity of tumour cells. Our results suggest that Stat3 is involved in the motility, metastasis and progression in human lingual squamous cell carcinoma, and thus, it may be a therapeutic target for human lingual squamous cell carcinoma. Copyright © 2012 John Wiley & Sons, Ltd.