Abstract: Sox gene family encodes a group of transcriptional factors and is defined by the presence of a highly conserved domain. Sox genes can be classified into several subgroups. The SoxD subgroup mainly consists of Sox5 and Sox6, which involve in the transcription regulation of development process including embryonic development, neural growth and chondrogenesis. Recent studies about the association between SoxD gene family and cancers are increasing and it suggests that SoxD gene family acts as tumor promoter or suppressor in distinctive cancers. Besides, the SoxD gene family can also act as diagnostic or prognostic markers in various tumors. In this paper, the structures and functions of Sox5/6 are introduced and recent advances in the role of Sox5/6 in cancers are summarized.