ABSTRACT:Nanotechnology is a new branch of science, which is going to be a major driving force behind the impending technological revolution in the 21st century. Although Doxorubicin (DOX) is one of the preferred chemotherapeutic drugs for the treatment of oral squamous cell carcinoma (OSCC), several studies pointed out that it was limited due to multidrug resistance (MDR) like the overexpression of DNA damage repair agents as poly (ADP-ribose) polymerase-1 (PARP-1). Accordingly, it seemed very interesting to explore the effect of DOX loaded mesoporous silica nanoparticles (MSNs) with their outstanding properties in comparison to the conventional DOX on HNO-97 cell line, in an attempt to introduce a novel efficient therapeutic modality for OSCC.