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Research on the development of higher order thinking problems based on problem solving on neural system material aims to produce higher order questions of thinking skills based on valid and reliable problem solving. The development of higher order problem thinking skills based on problem solving is based on the Anderson & Karthwohl and Polya frameworks. The problem developed is a multiple choice problem with five alternative answers. The evaluation process includes self-assessment, expert review, one-to-one and small groups. Readability questions are tested at the one-to-one stage. The results of the small group stages are then analyzed item items, namely item validity and item reliability. The validity of items is calculated using the product moment correlation, while the reliability of the questions is calculated using Anates 4.0. The results of the research conducted showed that the questions developed were valid and reliable. The results of this study can be used as a reference for teachers to provide higher order thinking problems based on problem solving and familiarize students with solving problems with these characteristics.