Background: Curcumin, a compound derived from the root of the Curcuma longa, has been confirmed as an anticancer, chemoprotective, and gene/protein regulatory agent. Nanoformulation of curcumin has been developed to increase its targeting efficiency, solubility, controlled release, and physical and chemical stability. Objectives: This study investigated the effect of new nano-type curcumin, oleic acid-derived dendrosome (OA400 nanoparticles), on the expression of E6 and E7 human papillomavirus oncogenes and P53 and Rb factors in the HeLa cell line. After preparing nano-curcumin by mixing OA400 nano-carrier and curcumin, its effect was considered on the human cervical cancer cell line (HeLa cell line RRID: CVCL_003) and normal fibroblast cells. Methods: MTT assay and flow cytometry were used to evaluate cell viability and apoptosis. Furthermore, real-time RT-PCR and western blot analyses assessed RNA and protein expression of E6, E7, P53, and Rb. Statistical analyses were performed by GraphPad Prism 7 software. Results: The nanoformulation of curcumin could reduce the expression of E6 and E7 oncogenes and increase P53 and Rb tumor suppressors in HeLa cancerous cells at 15 μM concentration; however, it had no significant effect on the viability of normal fibroblast cells. On the other hand, curcumin altered the expression of these genes at a 50-μM concentration. Gene and protein expression analysis indicated the up-regulation of P53 and Rb factors and the down-regulation of E6 and E7 under the influence of nano-curcumin treatment more than curcumin. Conclusions: These data indicate the potential of curcumin-loaded OA400 nanoparticles to be considered as a treatment option in cervical cancer investigations.