Background and Purpose: The transcription factor B cell lymphoma 6 (BCL6) is an oncogenic driver of diffuse large B cell lymphoma (DLBCL). Blocking the protein-protein interactions of BCL6 and its corepressors has been proposed as an effective approach for the treatment of DLBCL. However, BCL6 inhibitors with excellent drug-like properties are rare. Hence, the development of BCL6 inhibitors is worth pursuing. Experimental Approach: We screened our internal chemical library by luciferase reporter assay and Homogenous Time Resolved Fluorescence (HTRF) assay and a small molecule compound named WK500B was identified. The binding affinity between WK500B and BCL6 was evaluated by surface plasmon resonance (SPR) assay and the binding mode of WK500B and BCL6 was predicted by molecular docking. The function evaluation and anti-cancer activity of WK500B was detected by immunofluorescence assay, Real-Time Quantitative PCR, cell proliferation assay, cell cycle assay, cell apoptosis assay, enzyme-linked immunosorbent assay (ELISA) and animal models. Key Results: WK500B engaged BCL6 inside cells, blocked BCL6 repression complexes, reactivated BCL6 target genes, killed DLBCL cells and caused apoptosis as well as cell cycle arrest. In animal models, WK500B inhibited germinal centre (GC) formation and DLBCL tumor growth without toxic and side effects. Moreover, WK500B showed favourable pharmacokinetics and presented superior druggability compared to other BCL6 inhibitors. Conclusions and Implications: WK500B showed strong efficacy and favourable pharmacokinetics and presented superior druggability compared to other BCL6 inhibitors. So, WK500B is a promising candidate that could be developed as an effective orally available therapeutic agent for DLBCL.