Solid-phase extraction (SPE) based on trimethylsilyloxy-modified silica aerogel was developed for extraction of chemotherapeutic drugs from water. The developed method is easy and affordable, can be performed in separating funnel and does not require a vacuum and SPE manifold. The extraction and recovery of cyclophosphamide (CYP), dexamethasone (DEX), and paclitaxel (TAX) by the aerogel from water were investigated. The factors governing the extraction efficiency such as sample pH, sample volume, volume of eluent and concentration of analytes were studied. The LOD and LOQ of the developed method were calculated and linearity was found in the range of 4-100 μg L-1. The extraction efficiency of the aerogel was compared to that of other SPE cartridges, Oasis HLB, Strata-X-C, C18 and polymeric reversed phase, and the aerogel showed similar or better performance than the other commercial cartridges available on the market. The developed method was also used to extract chemotherapeutic drugs spiked in hospital wastewater.