The safflower plant as an attractive feedstock for development of a biorefinery through the multi-biofuel production was evaluated. The safflower plant, composed of straw (79.6 wt %) and oilseed (20.4 wt%), was used for bioethanol, biogas, and biodiesel production. The oil was extracted from the seeds and subjected to methanolic transesterification process to produce biodiesel. The remained seed cake was converted to biogas by anaerobic digestion process. The ethanol production from safflower straw was not satisfactory; thus, the straw was hydrothermally pretreated at 120-180 degrees C for 1-5 h to maximize the bioethanol production. The increase in the pretreatment time and temperature considerably improved the ethanol yield, and the highest yield of 60.3% was obtained performing the pretreatment at 180 degrees C for 5 h. The biodiesel and methane production yields from oilseeds and seed cake were 90.3% and 185.8 mL/g volatile solids, respectively. Overall, each kg of safflower plant yielded 97.2 g ethanol, 22.4 L methane, and 46.6 g biodiesel that are totally equivalent to 0.168 L gasoline per kg of safflower plant in this biorefinery concept. (C) 2020 Elsevier Ltd. All rights reserved.