Over 80% of the α-thalassemia cases in southern China are caused by large deletions involving the α-globin gene cluster on chromosome 16p13.3. Here, we characterized a novel 27.6-kb deletion on the α-globin gene cluster in a Chinese family. Its breakpoints were detected to lie between coordinates 9079 and 36718 of the α-globin gene cluster (NG_000006.1), with a total of 27,640 nucleotides deleted. It was designated as -α (27.6) deletion. The proband is a compound heterozygote of --(SEA) and -α (27.6) and he displayed very mild hemoglobin H disease phenotype with Hb 7.9-9.3 g/dl. Phenotypic analysis on heterozygote of this deletion revealed it as α(+) mutation. It leads to a very mild phenotype as adult heterozygotes have normal hematological parameters with the values at the lower border of the normal range. RT-PCR analysis showed that the α-globin mRNA level of the heterozygotes was decreased when compared with that of normal people.