Large intergenic noncoding RNAs (lincRNAs) are emerging as key factors of multiple cellular processes. Cumulative evidence has linked lincRNA polymorphisms to diverse diseases. However, the global properties of lincRNA polymorphisms and their implications for human disease remain largely unknown. Here we performed a systematic analysis of naturally occurring variants in human lincRNAs, with a particular focus on lincRNA polymorphism as novel risk factor of disease etiology. We found that lincRNAs exhibited a relatively low level of polymorphisms, and low single-nucleotide polymorphism (SNP) density lincRNAs might have a broad range of functions. We also found that some polymorphisms in evolutionarily conserved regions of lincRNAs had significant effects on predicted RNA secondary structures, indicating their potential contribution to diseases. We mapped currently available phenotype-associated SNPs to lincRNAs and found that lincRNAs were associated with a wide range of human diseases. Some lincRNAs could be responsible for particular diseases. Our results provided not only a global perspective on genetic variants in human lincRNAs but also novel insights into the function and etiology of lincRNA. All the data in this study can be accessed and retrieved freely via a web server at http://bioinfo.hrbmu.edu.cn/lincPoly.