Oral squamous cell carcinoma (OSCC) is among the ten most frequent human malignancies1,2 and is the most common malignancy of head and neck cancer.3 Advanced oral cancers can cause significant morbidity and mortality4. This OSCC is highly invasive and destroys tissues thus causing disfigurement, loss of function, pain, bleeding and necrosis.5 It is an established fact that tobacco, smoking, alcohol consumption alone or with chewing tobacco, and betel quid are potential carcinogens contributing to the high occurrence of OSCC.6,7 Interestingly, high incidences of OSCC have been reported in developing countries are due to different forms of smokeless tobacco exposure.8 Oral squamous cell carcinoma has a very poor prognosis, and it is often characterized by aggressive local invasion, early metastasis and poor response to chemotherapy.3 Current treatment modalities for OSCC include chemo or radiotherapy, surgical removal of cancer, treatment with epidermal growth factor receptor inhibitors and cyclooxygenase-2 inhibitors, and photodynamic therapy have led to the major problems related to non-specific cell death.9,10 However, none of these therapies are curative but merely symptomatic and as such these treatments produce only temporary clinical benefit. Hence, continue to identify the key agents that control tumor to deteriorate and thereby development of novel treatments that can block or inhibit invasion and/or metastasis is important for improving the prognosis of OSCC. Accordingly, several plants derived and synthetic compounds have been tested for their anticancer potential in experimental animals and in vitro OSCC cell lines and came out with promising results.11-13 In vitro context, these compounds selectively targets cancer cells and inhibits their proliferation and induced cytotoxicity via apoptosis and these effects are implicated as their beneficial effects against cancer.12-16 Natural bioactive substances have been reported to modify the redox status and interfere with basic cellular functions cell cycle, apoptosis, inflammation, angiogenesis, invasion and metastasis.17 Several studies have shown that natural products have a wide spectrum of biological activities including anti-inflammatory, antioxidant, antimutagenic and anticancer properties.18,19 Hence, in this study, we evaluated the cytotoxic effect of syringic acid in SCC -25 cell line.Syringic acid (SA), a known phenolic acid used in traditional Chinese herbal medicine and is an emerging nutraceutical.20 Several recent studies were reported SA potential as a hepatoprotective and antiinflammatory, antimitogenic, anti-hyperglycemic, neuroprotective, and memory-enhancing properties in various animal models.21-24 Cytotoxic effect of SA has been explored in several cancer cell lines other than human OSCC lines.20,23,25,26 Though SA has studied against various cancer types in vitro, its efficacy against human oral squamous cell carcinoma is not available. Hence, this study has been conducted with the objective to explore the anticancer efficacy of SA against oral squamous cell carcinoma SCC-25 cell.