The proliferating nuclear antigen (PCNA) is a crucial component of the DNA replication machinery. Replicative DNA polymerases bind to PCNA to efficiently achieve duplication of the genomic material. PCNA also promotes auxiliary DNA replication events such as Translesion DNA Synthesis (TLS), a DNA replication transaction that involves specialized polymerases (S-Pols) to replicate damaged DNA. Because cancer cells do not stop DNA replication cycles, even in the presence of DNA damage, it has been proposed that TLS is a good target for cancer therapy. However, inhibiting TLS is challenging because TLS Polymerases compensate for each other. Indeed, specific inhibitors of TLS polymerases do not block the TLS process globally. An alternative possibility to inhibit TLS is to block the interaction of all TLS polymerases with PCNA at once. We have previously shown that the stable expression of the cyclin kinase inhibitor, p21, does so through PCNA binding. Here we tested if a small peptide comprising the PCNA binding region of p21 achieves TLS polymerase displacement from PCNA. Our results indicate that a short peptide comprising the C-ternminal PCNA interacting region of p21 displaces all S-pols from PCNA and sensitizes cells to different treatments including cisplatin, chk1 inhibitors and Olaparib. Such observation was recapitulated when using a small peptide corresponding to the PCNA binding region of the S-Pol eta. These results suggest that small peptides with high affinity for PCNA capable of displacing PCNA partners such as S-Pols are versatile tool that can be used to sensitize tumour cells to different genotoxins.