Several recent investigations show that HOX transcript antisense intergenic RNA (HOTAIR) play an important role in the pathogenesis of different cancers. HOTAIR polymorphisms has been widely studied in the context of association between with the risk of cancer pathogenesis. However, there is no certain conclusion about the role of HOTAIR polymorphisms in different cancer initiation and progression. Our team has selected eligible studies up to 1 May 2019, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. We have included total number of 102 case–control investigations extracted from 41 eligible articles for the current meta-analysis. We calculated pooled odds ratio (ORs) with their corresponding 95% confidence intervals (CIs) using either fixed-effect or random-effect models for quantitative evaluation of the strength for the association between HOTAIR gene polymorphisms and the risk of cancer. Our current meta-analysis investigation showed that HOTAIR rs4759314 polymorphism particularly increased the overall risk of cancer in different models including homozygous, recessive and allele genetic. HOTAIR rs920778 significantly raised the cancer risk only in recessive genetic model. HOTAIR rs12826786 polymorphism was associated with cancer development in heterozygous, homozygous, dominant, recessive and allele genetic models. Also, an increase in cancer risk was observed with rs874945 polymorphism of HOTAIR gene in heterozygous, dominant and allele genetic models. The rs12427129 polymorphism showed correlation with cancer susceptibility only in recessive model. Subgroup analysis based on cancer type suggested that rs4759314 polymorphism significantly increased the risk of gastric and cervical cancers, and the rs920778 polymorphism increased the risk of gastrointestinal, cervical and gastric cancers. In summary, this study found that HOTAIR polymorphisms are significantly associated with cancer development.