Conventional anticancer therapies present low specificity, leading to several secondary effects. To improve these drawbacks, aptamers able to fold into G-quadruplex, with higher stability, are being used to promote drugs accumulation in cancer cells. AS1411 is a G-quadruplex aptamer able to recognize nucleolin, a protein overexpressed in cancer cells surface. This aptamer was tested in phase II clinical trials, but due to low response rates and suboptimal pharmacokinetics the trial was discontinued. Nevertheless, AS1411 is being used as a drug delivery for cancer. Moreover, AS1411 derivatives have been proposed, with improved toxicity and high affinity to nucleolin. In this sense, we propose to use AS1411 derivatives-functionalized liposomes to improve the selectivity of Imiquimod and C₈ into oral cancer. Thus, we synthesized liposomes functionalized with NH₂-aptamers(AS1411, AT11 and AT11-B0) and loaded with Imiquimod and C₈. The resulting liposomes were characterized by dynamic light scattering(DLS) and transmission electronic microscopy(TEM). The functionalization efficiency was determined by UV/Vis spectroscopy. Through the different steps of the synthesis, a gradual increasing of their size was observed, and functionalization yields up to 88% were obtained. Liposomes with sizes up to 200 nm were synthesized to be used as a potential anticancer therapy for oral cancer. In vitro studies demonstrated that C₈ and Imiquimod presented a IC₅₀ of 0.201 µM and 30.11 µM, respectively, in oral cancer cells. Through this methodology we expect to improve the selectivity of Imiquimod and C₈ into oral cancer cells and to decrease the toxicity in normal epithelial cells.