One of the most commonly drugs used for triple-negative breast cancer (TNBC) treatment is Paclitaxel (PTX), a chemotherapeutic agent. However, due to its non-selective mechanism, PTX causes numerous side effects, which limit its use and dosage. Dyskerin Pseudouridine Synthase 1 (DKC1) is involved in several cellular functions, including the proper assembly of the telomerase complex, RNP biosynthesis, and the regulation of specific RNAs and microRNAs. To develop new anti-cancer treatments, we previously used docking-based virtual screening to create R1D2-10, a novel DKC1 inhibitor. R1D2-10 inhibited cell proliferation and telomerase activity in breast cancer (BC) cell lines, resulting in telomere shortening, senescence, and apoptosis. In this study, database analysis revealed that DKC1 is overexpressed in BC tissue compared to healthy tissue, correlating with lower survival rates. TNBC showed the highest DKC1 expression among BC subtypes, with even higher levels in patients treated with PTX, indicating DKC1 as a potential target for TNBC treatment. We investigated the combined effect of R1D2-10 and PTX in MDA MB 231 and MDA MB 468 TNBC cell lines. Our findings demonstrated a synergistic effect on cell proliferation inhibition at various concentrations (1-20 µM/nM for R1D2-10 and PTX, respectively). Flow cytometry analysis showed a significant increase in Sub-G1 and G2/M populations, indicating cell cycle arrest. Additionally, the combined treatment elevated apoptosis levels, evidenced by increased Caspase 3/7 activity. RT-qPCR analysis revealed higher expression of pro-apoptotic genes bax/bcl2 and the cell cycle inhibitor p21 compared to monotherapy. These promising results support the development of a combined therapy with R1D2-10, aiming to reduce PTX doses and associated side effects. We are conducting further studies to confirm the clinical potential of R1D2-10 for TNBC treatment.