While platinum-based chemotherapy, radiation therapy and or surgery are effective in reducing human papillomavirus (HPV) driven cancer tumours, they have some significant drawbacks, including low specificity for tumour, toxicity, and severe adverse effects. Though current therapies for HPV-driven cancers are effective, severe late toxicity associated with current treatments contributes to the deterioration of patient quality of life. This warrants the need for novel therapies for HPV derived cancers. In this short review, we examined RNA-based therapies targeting the major HPV oncogenes, including short-interfering RNAs (siRNAs) and clustered regularly interspaced short palindromic repeats (CRISPR) as putative treatment modalities. We also explore other potential RNA-based targeting approaches such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and mRNA vaccines as future treatment modalities for HPV cancers. Some of these technologies have already been approved for clinical use for a range of other human diseases but not for HPV cancers. Here we explore the emerging evidence supporting the effectiveness of some of these gene-based therapies for HPV malignancies. In short, the evidence sheds promising light on the feasibility of translating these technologies into a clinically relevant treatment modality for HPV derived cancers and potentially other virally driven human cancers.