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To fostering 21st century skills, lecturers must implement a lesson toward a high-level questioning skills as a target. Higher Order Questions (HOQs) emphasize on application, analysis, synthesis, and evaluation. However, unfortunately to date, HOQs have not received adequate attention from lecturers and researchers. This research was aimed to analyze the effect of use of phylogenetics approach in Angiosperm taxonomy learning on HOQs and critical thinking of undergraduate students. This research was conducted on the 4th semester Biology students which are consisted of 27 students. Research method was pre-experimental with one group pretest posttest design. The results indicated that there is improvement of students HOQs (N-Gain= 62.4%) as well as their critical thinking (N-Gain= 62.1%). In addition, qualitative data revealed of the increasing from LOQs to be HOQs. Good achievement of step by step of learning process using phylogenetic approach experienced by each student was well documented in this study.