Microwave hydrothermal liquefaction (MHTL) was introduced to transform watermelon peel to 5-hydroxymethylfurfural (HMF), a top value added chemical from biomass. The key MHTL process parameters of holding temperature, holding time, and liquid-to-solid ratio were optimized by a Box-Behnken design and response surface methodology. The highest HMF yield (3.8%) was obtained with a holding temperature of 135 degrees C, holding time of 6 min, and liquid-to-solid ratio of 12:1, respectively. The economic evaluation showed that 1.52 kg of HMF could be obtained from 1 t of fresh watermelon peel under the optimum MHTL conditions. It indicates a feasible and environmental friendly waste valorization method. (C) 2019 Elsevier Ltd. All rights reserved.