Lung squamous cell carcinoma (LUSC) is one of the most common subtypes of lung cancer that accounts for ~50% of all lung cancer cases. Long noncoding RNA (lncRNA) PSMG3-antisense (AS) 1 has been suggested to play an important role in various types of cancer. Therefore, the aim of the present study was to investigate the role of PSMG3-AS1 using clinical specimens and data from 130 patients with LUSC. The expression levels of PSMG3-AS1 and miR-143-3p were detected in LUSC specimens, and the correlation between lncRNA PSMG3-AS1 expression and patient clinical characteristics was analyzed. Cell Counting Kit-8, Transwell migration and invasion assays were used to investigate the functional role of PSMG3-AS1 in LUSC. The mechanism of PSMG3-AS1 on LUSC cells was also investigated using a luciferase activity assay with wild-type or mutated PSMG3-AS1. PSMG3-AS1 was found to be upregulated in LUSC, and high expression was associated with positive lymph node metastasis and a higher TNM stage. The results of multivariate Cox regression analysis revealed that PSMG3-AS1 may serve as an independent prognostic indicator in LUSC. Furthermore, inhibiting PSMG3-AS1 expression reduced tumor cell proliferative, migratory and invasive abilities. Moreover, PSMG3-AS1 was found to be closely associated with miR-143-3p in LUSC, and thus may become a potential prognostic marker and therapeutic target for the treatment of LUSC in the future.