Updated project metadata. We have investigated the proteome changes induced by SOX4 overexpression in HCT-116 cells using iTRAQ-based quantitative proteomics. Bioinformatics analysis revealed that HDAC1 could be one of the important regulators in cancer stem cells (CSCs) maintenance. We found that SOX4 transcriptionally regulates HDAC1 to support the stemness of cancer stem cells (CSCs). This work revealed a novel underlying mechanism, SOX4-HDAC1 axis, for stemness maintenance of human cancer.