Safranal, a bioactive component of a traditionally used spice and condiment saffron possesses a wide spectrum of biological properties, including antitumor activities. It has been shown to inhibit the proliferation and growth of prostate cancer cells by inducing apoptosis. However, the ability of safranal to modulate the Epithelial-Mesenchymal Transition (EMT) which is indispensible to the invasiveness and metastasis of oral squamous cell carcinoma remains to be elucidated. The aim of this study was to determine whether safranal affects EMT in oral squamous cell carcinoma cells. The results showed that safranal not only inhibited oral squamous cell carcinoma cell proliferation, migration and invasion in a dose-dependent manner but also modulated the expression of EMT-related proteins E-cadherin and vimentin which are indespensible to cellular motility, invasiveness and metastasis. Taken together, our results indicate that safranal suppresses oral squamous cell carcinoma cell migration and invasion by modulating the expression of EMT proteins. The study thus suggests that safranal may serve as a potential anticancer agent for oral squamous cell carcinoma.