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Background The comparative study of chromatin open state of various cells and tissues is helpful for dissecting the epigenetic causes of various biological and pathological processes such as development and tumorigenesis. This study comparatively characterized the chromatin open regions (CORs) of two normal human cell lines (HL7702 and MRC-5), nine human cancer cell lines (GM12878, HepG2, PANC-1, A549, HT29, SKOV3, SiHa, C-33A, and HeLa), one mouse cancer cell line (Hepa1-6), and healthy mouse liver tissue with SALP-seq.Results This study therefore made a set of systematic and useful COR profiles of human and mouse cells and tissues. These COR profiles were used to explore the possible epigenetic bases of several interesting scientific problems, including how chromatin state changes contribute to tumorigenesis, how the cancer-related mutation hotspots are formed, why fibroblast was most widely used to prepare iPSCs, and how HPV subtypes differently affect the chromatin structure of cervical cells. The results revealed that the comparative COR profiling can shed new insights into the potential molecular mechanisms underlying these important biological and pathological processes. The comparative COR profiling also demonstrated transcription factors differentially dominate various biological and pathological processes. At last, the comparative COR profiling uncovers new potential markers or targets for cancer diagnosis and therapy.Conclusions The comparative COR profiling with our developed SALP-seq technique can be used to uncover epigenetic bases and molecular mechanisms underlying various biological processes.