Objective To investigate the distribution of mutations of common deaf related genes GJB2, SLC26A4, mitochondria 12SrRNA and GJB3 in 246 patients with deafness in xi 'an and provide support for finding a genetic counseling model suitabling for the population in this region. Methods Microarray was used to screen 9 hotspots of four common genetic deafness genes in 246 patients with non syndromic deafness in xi 'an. In the follow up genetic counseling, a further family investigation was conducted, and the complete exon sequence analysis of GJB2 and SLC26A4 genes was treated. Results Among 246 patients with deafness, the detection rate of gene mutation was 34.55% (85/246), including GJB2 gene mutation 17.48%(43/246), SLC26A4 gene mutation 14.23%(35/246), and mitochondrial DNA 12SrRN A1555A＞G homogeneous mutation 2.85% (7/246). In addition, the results of family investigation showed that the mutation carrying rate of GJB2 and SLC26A4 gene was 48.72% (19/39). Finally, the complete exon sequence analysis of GJB2 and SLC26A4 genes revealed additional mutation loci on GJB2 genes, including c.605ins46, c.79G＞A, c.341A＞G, c.257C＞G, and c.109G＞A. Conclusion Gene screening of 246 patients with deafness in xi 'an should be mainly based on mutations of GJB2 and SLC26A4 genes. In addition, it should not neglect the important role of comprehensive pedigree investigation and timely combined exon sequence analysis of GJB2 and SLC26A4 genes in personalized genetic counseling such as follow up diagnosis, treatment, life and marriage and parenting guidance.