INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with high mortality rate. Conventional treatment strategies have improved but remain far from optimal. Cancer research is focused on improving cancer diagnosis and treatment methods using nanotechnology, by the production and application of nanoscale drug delivery systems. In medicine, several types of nanoparticles have evolved, gold nanoparticle (AuNPs) are an excellent candidate as drug delivery vehicle due to their favorable chemical and optical properties. Paclitaxel (PTX) is an effective antineoplastic drug that has a wide spectrum of antitumor activity, against head and neck malignancies. The encapsulation of PTX in nanodelivery systems can protect the drug from degradation during circulation and protect the body from its toxic side effects. OBJECTIVES: To study the therapeutic efficacy of PTX-functionalized AuNPs versus the free form of the drug. Also the study will evaluate the treatment, by the use of proliferative immune-histochemical marker (PCNA). MATERIAL AND METHODS: Squamous cell carcinoma will be chemically induced in sixty Syrian hamsters. Then they will be divided into three groups, 20 in each. One group will be treated with free PTX, another group will be treated with PTX-AuNPs, and the last group will be given saline as negative control group. RESULTS: Group treated by PTX loaded on AuNPs showed significant results over group treated by free PTX. CONCLUSIONS: The unique AuNPs properties in combination to the chemotherapeutic drug target cancer cells while maintaining no adverse effects on the surrounding normal cells.