Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell cycle control, and embryonic development. We performed structural study on human TIP60 complex with cryo-electron microscopy. The structural model of human TIP60 complex was built based on the high-resolution cryo-EM maps, assisted by cross-linking mass spectrometry (CX-MS) and AlphaFold2 prediction.