The Sin3/HDAC multi-protein complex consists of at least 17 subunits and is known to have roles in diverse biological and cellular processes including transcription, chromatin structure, and the cell cycle. ING2 is a non-catalytic component of this complex. To obtain a better mechanistic understanding of the Sin3/HDAC complex in cancer, we extended its protein-protein interaction network and identified a mutually exclusive pair within the complex. Suberoylanilide hydroxamic acid (SAHA) is an FDA approved HDAC inhibitor used for the treatment of cutaneous T-cell lymphoma. We assessed the effects of SAHA on the disruption of the complex network through six homologous baits. SAHA perturbs multiple protein interactions and therefore compromises the composition of large parts of the Sin3/HDAC network. A comparison of the effect of SAHA treatment on gene expression in breast cancer cells to a knockdown of the ING2 subunit indicated that a portion of the anticancer effects of SAHA may be attributed to the disruption of ING2s association with the complex.