Abstract Introduction- Cancer, an heterogeneous condition, arises through mutations in the tumor suppressors and proto oncogenes which are otherwise involved in numerous cellular processes.These mutations rewire the signaling cascades to promote ‘malignant phenotype'. Under such circumstances the DNA repair system aids in rectifying the mutations and establishing normalcy.Plant derived products have shown promising success in treatment of cancer. In the present study, we make an attempt to screen various curcumin compounds to identify putative targets related to hematologic malignancies which in turn modulate the functionally altered mismatch repair system (MMR) using computational tools. Methods-A total of 536 curcumin compounds, retrieved from peer reviewed literature and black turmeric database, were analyzed for molecular characteristics, biological activities, ADME/Tox and, drug-like properties through Molinspiration and PreADMET. This was followed by prediction of site of metabolism via FAME3SOM tool. Simultaneously, COSMIC database was used for selection of proteins associated to haematologic malignancies. The database helped us to identify 9 proteins viz. abl1, max, myb, myc, pcna, p73, top3a, blm and vbp1; molecular aberrations of which are associated with malignant transformation in blood related cancers. Additionally, STRING identified these proteins having significant interaction with proteins of mismatch repair system. The crystal structures of the proteins were obtained from PDB and their domains and active sites were predicted using scanPROSITE, MOTIF Search, metaPOCKET2 and PrankWeb tools. Finally the proteins and ligands were energy minimized using YASARA and subjected to virtual screening and molecular docking using Autodock Vina and Autodock Tools respectively. Results-The overall results revealed six of the curcuma compounds (two monocarbonyl derivatives, one non-curcuminoid and three black turmeric natural compounds) may have the potential to modulate the identified targets and thus revive the MMR functionality; rescuing the genome from being unstable. Conclusion-With these analyses we predict that curcumin compounds can modulate therapeutic targets identified here and in turn rescue the function of MMR in hematologic malignancies. Citation Format: Priyanjali Bhattacharya, Trupti N. Patel. Anticancer potential of curcuma and target identification in hematologic malignancies: A focus on mismatch repair [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 170.