Objective:TSLC26A4 gene is thought to be the second major contributor to hereditary hearing loss. At least 170 pathological mutations of SLC26A4 were identified in deafness patients,and showed regional differences and ethnic specificity for different groups around the world. However,no unanimous conclusion was achieved on the high frequency mutations of SLC26A4 which induced the hearing loss. This study is aimed to invistigate the molecular structure and racial difference of high frequency pathological SLC26A4 mutations in hearing loss. Methods: Total of 662 published epidemiological studies of SLC26A4 mutation and deafness was collected from 1997,Jan to 2014,Dec. through the databases. Based on the NOS standard,31 of the articles were included. meta-analysis was carried to study the data of SLC26A4 mutation frequency. Stata11.2 and RevMan 5.1 software was used to describe the data of literature for meta-analysis to explore deaf risk correlation. Swiss Model software was used to analyze the molecular structure of high frequency pathological SLC26A4 mutations. Results: ①A variety of types of SLC26A4 mutations are associated with an increased deafness risk(OR= 39.73,95% CI: 21.359-73.903,P < 0.0001);② It indicates the significant heterogeneity in Asian but not in European and American;③Particularly,the 6 kinds of mutations were calculated as high frequency pathological SLC26A4 mutations (p.V138F,p.G209V,IVS7-2A>G,IVS8+1G>A,p.T416P and p.H723R),protein structure changes of which were simulated by Swiss Model. Conclusion: These findings advance our knowledge of the genetic basis of SCL26A4 variation with hereditary hearing loss in the multiethnic populations