A method to trigger in-device coexistence (IDC) interference mitigation is provided. A wireless device comprises a first radio module and a co-located second radio module. The first radio module measures a received radio signal based on a plurality of sampling instances. A control entity obtains Tx/Rx activity of the second radio module and informs Tx/Rx timing information to the first radio module. The first radio module determines a measurement result based on the obtained timing information. The first radio module triggers an IDC interference mitigation mechanism if the measurement result satisfies a configurable condition. In one embodiment, the first radio module reports IDC interference information and traffic pattern information of the second radio module to a base station for network-assisted coexistence interference mitigation. The IDC triggering mechanism prevents unnecessary and arbitrary IDC request from the device and thus improves network efficiency.