Oral cancer is one of the most significant cancers in the world; the most common of which is oral squamous cell carcinoma (OSCC) that makes up to 94% of oral malignances (Bernestein et al, 2013). Based on reports of the world Health Organization (WHO), OSCC occupied the sixth most common cancer in the world, Despite the advances and extensive research on novel approaches, current treatments are still limited to surgery, radiotherapy and conventional chemotherapy (Rosenthal et al, 2016). To date, chemotherapy is one of the most effective treatments (Wang et al, 2015). Among the most important anti-neoplastic drugs, anthracycline antibiotic doxorubicin (DOX) is commonly used in cancer therapyIn the past few years, the research field of nanomedicine has rapidly developed great promises in fighting cancer, and held the hope of providing new selective methods which can destroy cancer cells without harming healthy tissues (Zardini et al, 2015). Silica nanoparticles are among the most promising organic nano-biomaterials which were approved by the US Food and Drug Adminstration (FDA) for cancer therapy clinical trials (Wang et al, 2018). They have many advantages including their tunable particle size ( from 50-300 nm) which facilitate endocytosis by living cells, in addition to large pore volume and surface area for better control over drug loading and release (Zhou et al, 2018).