Maturity-Onset Diabetes of the Young (MODY) is a monogenic form of diabetes mellitus characterized by autosomal dominant inheritance, early age of onset, and pancreatic beta cell dysfunction. Six MODY genes represent an excellent candidate gene set for identification genetic variation in the MODY family. There is no prior study on the molecular genetics of early-onset type II diabetes in Xinjiang Uighur Autonomous Region and also there is no report on mutations in MODY genes in Uighur ethnic population. The screening for mutations and polymorphism in six known MODY genes (HNF4α, GCK, HNF1α, IPF1, HNF1β, and NEUROD1) in a Uighur family with clinically diagnosed with MODY are studied. One Uighur MODY family from Kashgar City of Xinjiang was involved in this research with its informed consents. Proband and his father were screened for mutations and polymorphism in exon and exon-intron boundaries of six known MODY genes by PCR method followed by direct DNA sequencing. All sequences were analyzed and compared with the reference sequence from NCBI with the Lasergene software (DNASTAR). Seventeen sequence variations are identified and none of them are classified as the pathogenic mutation. Sequence variants of HNF1α gene are relatively more common. HNF1α Exon7 p.Gln497Gln, and NEUROD1 Exon1 c.164G>A are novel variations. Others are all previously described common polymorphisms. No pathogenic mutations or polymorphisms found in GCK. In summary, it is the first report in which six known MODY genes are screened for mutations in Uighur ethnic group. Mutations in MODY1-6 genes might not be the cause of this MODY family. The negative results in MODY genes are provided a further support for the high heterogeneity of this disease. This is the first step for the researches on the MODY genes in Uighur MODY family. The variations which are identified in the study might indicate a relatively high susceptibility to MODY or Type II DM for the Uighur population.