X-linked inhibitor of apoptosis (XIAP) is a member of the inhibitor of apoptosis (IAP) family and involved in the suppression of apoptosis in cancer cells. This property makes it a therapeutic target for the cancer therapy. In the present study, we developed QSAR models using chemical descriptors, fingerprints, principal components, docking energy parameters and similaritybased approach against XIAP. We achieved correlation (R) of 0.803 with R2 value of 0.645 at 10-fold cross validation using SMOreg algorithm. We evaluated these models on independent dataset to ascertain its robustness and achieved correlation (R) of 0.793 with R2 value of 0.628. Further, we used these models for the screening of FDA approved drugs and drug-like molecules from ZINC database and prioritized them on the basis of their predicted pIC50 values. Docking studies of top hits with XIAP-BIR3 domain shows that Iodixanol (DB01249) and ZINC68678304 have higher binding affinities than well-known tetrapeptide inhibitor, AVPI. We integrated these models in a web server named as “XIAPin”. We hope that this web server will contribute in the designing of nifty antagonists against XIAP. © 2015 Bentham Science Publishers.