Microarray and qRT-PCR showed that the level of HOXA11-AS was significantly higher in LSCC than that in the corresponding adjacent non-neoplastic tissues. ISH revealed that HOXA11-AS was strongly expressed in the nucleus and closely related to the T grade, neck nodal metastasis, and clinical stage. Patients with T3-4 grade, neck nodal metastasis, or advanced clinical stage presented a high HOXA11-AS expression. Kaplan-Meier analysis showed that high HOXA11-AS expression could predict a poor prognosis in LSCC patients. Furthermore, HOXA11-AS knockdown significantly inhibited the growth, migration, and invasion of LSCC cells.we speculated that HOXA11-AS might function through binding to proteins, such as transcription factors, in order to regulate the downstream genes.