21 st -century education requires students to have critical thinking skills. This research aim was to analyze the influence of the guided inquiry learning model assisted by student worksheets based on Higher Order Thinking Skills (HOTS) on students' critical thinking skills during online learning at Senior High School 1 Gadingrejo class XI Science Major. This research used a quasi-experiment design with a pretest-posttest non-equivalent control group design. The samples in this study were students of the Natural Science Major class, XI Science Major 2 as the control class, and XI Science Major 7 as the experiment class, which was selected through the purposive sampling technique. The research data consist of quantitative and qualitative. Quantitative data from the average pre-test, post-test, and N-Gain score as a result of critical thinking skills were analyzed by an independent sample t-test (α=0.05) using SPSS 25.0 For Windows. The results showed a significant effect of applying the HOTS-based guided inquiry learning model on students' critical thinking skills during online learning (Sig. 0.010 < 0.05). The experiment class N-gain value of 0.65 is classified as a medium category. Qualitative data in the form of a questionnaire on the implementation of online learning with an average percentage result of 64.2% is included in the strong category. 92% of students agree that the difficult questions in the HOTS-based worksheets help improve critical thinking skills. Therefore, the guided inquiry learning model assisted by HOTS-based worksheet students affects students' necessary thinking skills during online learning.This is an open access article under the CC-BY-SA license.