Purpose It is becoming evident that long non-coding RNAs (lncRNAs) participate in diverse biological processes via distinct mechanisms. Many lncRNAs have altered expression and likely to have functional roles in tumorigenesis. Although loss of maternally-expressed gene 3 (MEG3) expression has been detected in non-functioning pituitary adenomas (NFPAs), there are no published reports regarding the association between MEG3 expression and the invasive ability of NFPAs. Moreover, the roles of Hox transcript antisense intergenic RNA (HOTAIR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in NFPAs have not been examined. To investigate the role of MEG3, HOTAIR, and MALAT-1 in NFPA development and invasion. Methods MEG3, HOTAIR, MALAT-1 and proliferating cell nuclear antigen (PCNA) were detected in 52 NFPA samples and seven normal human anterior pituitaries using real-time quantitative reverse transcription polymerase chain reaction. Results MEG3 lncRNA levels gradually decreased whereas HOTAIR lncRNA levels gradually increased from normal anterior pituitaries to non-invasive NFPAs to invasive NFPAs. There was a significant association between MEG3 (P<0.01) and HOTAIR (P<0.05) expression and the biological behavior of the tumor. Furthermore, PCNA mRNA levels markedly increased in invasive NFPAs compared to non-invasive ones (P<0.01). In addition, PCNA mRNA negatively correlated with MEG3 lncRNA levels (P<0.05). Conclusions MEG3 and HOTAIR expression may correlate with NFPA development and invasion.