The base excision repair pathway is essential in human cells to preserve genome stability. Emerging data highlight a role of the BER in the regulation of gene expression during tumor progression and chemoresistance through several transcriptional and post-transcriptional mechanisms. Notably, RNA is vulnerable to the same endogenous and exogenous damage sources as DNA, including oxidation and alkylation, which can profoundly affect the chemical and biological properties of RNA molecules within cells. Recently, an involvement of BER enzymes in RNA processing has been proposed, possibly elucidating their impact in gene expression regulation. Moreover, the detection of oxidized RNA is a common feature of ageing and neurodegenerative diseases. Since some BER enzymes display quality-control activities over oxidized and abasic RNA, it is plausible to consider BER as a powerful prognostic and predictive factor in several human pathologies. This chapter will describe the canonical activities of BER factors in DNA repair with a particular emphasis on some emerging aspects related to gene expression. These novel functions and regulation of BER enzymes could explain their role in human pathologies.