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Graphical abstract, RNA modifications, in particular N6-methyladenosine (m6A), participate in every stages of RNA metabolism and play diverse roles in essential biological processes and disease pathogenesis. Thanks to the advances in sequencing technology, tens of thousands of RNA modification sites can be identified in a typical high-throughput experiment; however, it remains a major challenge to decipher the functional relevance of these sites, such as, affecting alternative splicing, regulation circuit in essential biological processes or association to diseases. As the focus of RNA epigenetics gradually shifts from site discovery to functional studies, we review here recent progress in functional annotation and prediction of RNA modification sites from a bioinformatics perspective. The review covers naïve annotation with associated biological events, e.g., single nucleotide polymorphism (SNP), RNA binding protein (RBP) and alternative splicing, prediction of key sites and their regulatory functions, inference of disease association, and mining the diagnosis and prognosis value of RNA modification regulators. We further discussed the limitations of existing approaches and some future perspectives.