Long non‑coding RNAs (lncRNAs) have been increasingly recognized as important immune checkpoints involved in the pathogenesis of autoimmune diseases. However, the exact role of lncRNAs in Hashimoto's thyroiditis (HT) has been rarely studied. The aim of the present study was to investigate the role of lncRNAs and the potential biomarkers in HT, a total of 33 patients with HT and 32 healthy volunteers were enrolled in the present study, and five patients and five healthy controls were investigated using next generation sequencing. A total of 218 dysregulated lncRNAs, including 94 upregulated and 124 downregulated lncRNAs, were identified and examined in the peripheral blood mononuclear cells (PBMCs) from patients with HT. The majority of the lncRNAs were intergenic and exonic (66.06%). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that abnormally expressed lncRNAs were enriched in the 'NF‑kB expression', in the 'TGF‑β signaling pathway' and in the 'JAK‑STAT signaling pathway', which are associated with the immunopathogenic mechanisms of HT. In total, three lncRNAs (LOC729737, XLOC_I2_006631 and BC041964) were validated and had a trend identical to that detected by the sequencing results. The expression of lncRNA‑XLOC_I2_006631 was upregulated and was positively correlated with the serum concentrations of anti‑thyroperoxidase antibody in patients with HT. Methyl‑CpG‑binding protein 2 (MECP2) was identified as the potential regulatory gene of lncRNA‑XLOC_I2_006631 using a prediction program. The expression of MECP2 was increased and was positively correlated with the elevated expression levels of lncRNA‑XLOC_I2_006631 and anti‑thyroperoxidase antibody in patients with HT. Furthermore, lncRNA‑XLOC_I2_006631 was able to regulate MECP2 expression in vitro. Receiver operating characteristic curve analysis suggested that lncRNA‑XLOC_I2_006631 has a potential diagnostic value. Collectively, the present results indicated the important role of dysregulated lncRNAs in HT and demonstrated that lncRNA‑XLOC_I2_006631 functioned as a positive regulator of MECP2 expression, suggesting a potential mechanism. Thus, lncRNA‑XLOC_I2_006631 may be used as a biomarker of HT.