Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) is a popular assay method for studying genome-wide chromatin interactions mediated by a protein of interest. The main goal of ChIA-PET data analysis is to detect interactions between DNA regions. Here, we propose a new method and the associated data analysis pipeline, ChIAPoP, to detect chromatin interactions from ChIA-PET data. We compared ChIAPoP with other popular methods, including a hypergeometric model (used in ChIA-PET tool), MICC (used in ChIA-PET2), ChiaSig and mango. The results showed that ChIA-PoP performed better than or at least as well as these top existing methods in detecting true chromatin interactions. ChIAPoP is freely available to the public at https://github.com/wh90999/ChIAPoP.