Increasing evidence has shown that long non-coding RNAs (lncRNAs) serve a critical role in tumor progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) is associated with the progression of oral squamous cell carcinoma and multiple myeloma. However, the roles of lncRNA PDIA3P in non-small cell lung cancer (NSCLC) remain unknown. In the present study, it was demonstrated that lncRNA PDIAP3 expression was significantly increased in patients with NSCLC, particularly in patients with an advanced Tumor-Node-Metastasis stages and lymph-node metastasis. The Gene Expression Profiling Interactive Analysis database revealed that patients with NSCLC with high lncRNA PDIA3P expression had a poorer disease-free survival rate. Furthermore, functional assays suggested that PDIA3P inhibition significantly suppressed the proliferation and invasion of NSCLC cells in vitro and reduced tumor growth in vivo. In addition, lncRNA PDIA3P enhanced the activity of the Wnt/beta-catenin pathway in progression of NSCLC. The present study showed that lncRNA PDIA3P promoted NSCLC progression by regulating Wnt/beta-catenin signaling, highlighting a potential therapeutic target for treating patients with NSCLC treatment.