Human phospholipid scramblase I (hPLSCR1) is a proapoptotic protein whose expression is deregulated in a variety of cancers cells. However till date the transcription regulation of hPLSCR1 is unknown. Transcriptional regulation of hPLSCR1 was studied by cloning the 5'-flanking region of hPLSCR1. Luciferase assays revealed that -1525 to -1244 region of hPLSCR1 was found to regulate its promoter activity. A putative Snail transcription factor (TF) binding site was found within the regulatory region of the promoter. Snail binding was found to down regulate the expression of hPLSCR1 both at the transcriptional and translational levels. Snail knock down using Snail-shRNA confirmed that down regulation of hPLSCR1 by Snail was specific. Point mutation studies confirm that the predicted Snail TF binds to -1123 to -1117 site. ChIP assay further confirms the physical interaction of Snail with hPLSCRI promoter. This is the first report showing the transcriptional regulation of hPLSCR1 expression by Snail TF and its possible implications in cancer progression. (C) 2014 Elsevier Inc. All rights reserved.