In addition to several molecular and morphologic changes, epithelial-mesenchymal transition (EMT) cells also show variation in sensitivity to chemotherapeutics agents. The aim of this study was to investigate whether overexpression of Snail in MCF-7 cells is associated with facilitated acquisition of P-gp mediated multidrug resistance (MDR). The results demonstrated that over-expression of Snail indeed resulted in slight enhancement of adriamycin-induced MDR in MCF-7/Snail cells without detectable increase of P-gp. However, in the longer term, MCF-7 cells overexpressing Snail were prone to be resistant to adriamycin, in this case with increased expression of P-gp. These results provide evidence that a strategy involving Snail inhibition may be a useful and promising therapeutic aspect in modulating MDR.