The invention discloses a water-soluble celastrol derivative and an application thereof, wherein a chemical structure formula of the water-soluble celastrol derivative is represented as the formula (I). In the formula (I), the R is a C2-C12 acyl group and the M is Na, K, NH4 or Ca or the like. The water-soluble celastrol derivative can be used for preparing various pharmaceutical dosage forms with pharmaceutically acceptable carriers or auxiliary materials, such as injections, tablets, capsules, granules and liniments, especially as the injections. The derivative has an excellent anti-tumor activity, can be used for preparing an anti-tumor drug and especially for a drug for treating colon cancer.