Haematococcus pluvialis, a green microalga, can accumulate high level of astaxanthin which is regarded as a super antioxidant extensively used in cosmetics, poultry, food, and pharmaceutical industries. The difficult point for extraction of astaxanthin is how to break the thick resistant cell walls of Haematococcus pluvialis effectively. In this work, this difficulty was successfully solved by the biocompatible protic ionic liquids-based microwave-assisted liquid-solid extraction (PILs-MALSE). Ethanolammonium caproate (EAC), a PIL used in here, can strongly dissolve mannan, one of the main components of the cell walls of Haematococcus pluvialis, which can leave out the pretreatment process to disrupt the cell walls before extraction, thereby leading to fast extraction (extraction time, 50 s). Furthermore, EAC has the obvious advantages over the imidazolium-based ILs, such as low cost, easy synthesis, and excellent biocompatibility. The PILs-MALSE method is more effective for the extraction of astaxanthin compared with conventional extraction techniques.