Recent studies have shown contribution of long non-coding RNAs (lncRNAs) in the pathogenesis of a number of psychiatric disorders. In the current study, we investigated the association between a single nucleotide polymorphism in the lncRNA HOX transcript antisense intergenic RNA (HOTAIR) and risk of diverse neuropsychiatric conditions in Iranian population. The selected polymorphism (rs1899663) is an intronic variant of this lncRNA which has been associated with several cancers in different populations. This SNP was genotyped in 323 individuals with methamphetamine addiction, 55 children with attention-deficit hyperactive disorder (ADHD), 138 patients with bipolar disorder 1 (BPD1), 86 patients with BPD2, 53 patients with major depressive disorder (MDD), and 194 patients with schizophrenia (SCZ). There was no significant association between rs1899663 genotypes and risk of methamphetamine addiction or SCZ in any assessed inheritance model. There was a significant association between rs1899663 SNP and risk of BPD1 in allelic, co-dominant, and dominant models (P values of 0.003, 0.009, and 0.003, respectively). The T allele of this SNP conferred risk of BPD1 (OR (95% CI) = 1.70 (1.20-2.41)). This SNP was associated with risk of BPD2 in allelic and dominant models (P values of 0.02 and 0.04). The T allele of this SNP was revealed to be the risk allele for BPD2 as well (OR (95% CI) = 1.61 (1.09-2.40)). Besides, the mentioned SNP was associated with susceptibility to MDD in allelic and dominant models (P values of 0.01 and 0.03). Finally, the rs1899663 was associated with risk of ADHD in allelic, co-dominant, and dominant models (P values of 3.6E-4, 0.002, and 1.2E-4, respectively). The current investigation highlights the role of rs1899663 in conferring risk of BPD1, BPD2, MDD, and ADHD and suggests a similar underlying genetic background for these conditions.