Proteolysis targeting chimera (PROTAC) is an emerging protein degradation strategy, which shows excellent advantages in targeting those so-called "undruggable" proteins. However, the potential systemic toxicity of PROTACs caused by undesired off-tissue protein degradation may limit the application of PROTACs in clinical practice. Here we reported a radiotherapy-triggered PROTAC prodrug (RT-PROTAC) activation strategy to precisely and spatiotemporally control protein degradation through X-ray radiation. We demonstrated this concept by incorporating an X-ray inducible phenyl azide-cage to a bromodomain (BRD)-targeting PROTAC to form the first RT-PROTAC. The RT-PROTAC prodrug exhibits little activity but can be activated by X-ray radiation in vitro and in vivo. Activated RT-PROTAC degrades BRD4 and BRD2 with a comparable effect to the PROTAC degrader and shows a synergistic antitumor potency with radiotherapy in the MCF-7 xenograft model. Our work provides an alternative strategy to spatiotemporally control protein degradation in vivo and points to an avenue for reducing the undesired systemic toxicity of PROTACs.