Spaceflight solid waste (SSW) is different from terrestrial municipal solid waste since it contains quite amount of medicines needing co-disposal sometimes. Harmless co-disposal of the hazardous drug discarded into SSW is extremely important for safe operation of the Environmental Control and Life Support System (ECLSS) during long-term space missions. In this work, hydrothermal oxidation (HTO) process was proposed for detoxification and mineralization treatment of the blend waste comprising of SSW and waste drugs (diclofenac sodium, DS). The results showed that a large number of toxic chlorinated organics were detected in the hydrothermal process without oxidant. On the contrary, in the presence of oxidant (H2O2), an efficient dechlorination and detoxification level was achieved above 300 degrees C. The optimal conditions including temperature, time and H2O2/waste (H/S) ratio were 300 degrees C, 30 min and 30 mL/g, respectively. The dechloridation efficiency and carbon conversion efficiency under the optimal conditions were over 95% and 77%, respectively. Furthermore, a suitable concentration of nitrate, TOC and COD were also obtained under the optimal conditions, implying that the byproducts after the HTO process exhibited the potential for plant growing in the ECLSS. Compared with other oxidation techniques for waste disposal in space, HTO process exhibited significant technical advantages of disposing the blend waste containing waste medicines and SSW. Accordingly, HTO process was recommended as a promising, efficient and environment-friendly method to dispose spaceflight solid waste containing various types of hazardous matters during long-term space missions.