Background and Aim: adaptation refers to all the strategies that a person uses to manage stressful life situations, whether they are real or unreal threats. The purpose of this study is to determine the effect of life skills training on the adaptation of high school girls and its relationship with health literacy. Materials and Methods: This study was conducted by an intervention method on 120 students (60 in the intervention group and 60 in the control group) of secondary school girls in the second stage of Sanandaj city in 2023 using a multi-stage sampling method. Life skills training was conducted in twelve 45-minute sessions by lecture, group discussion, question and answer method. To collect information, a student adaptation questionnaire and a standard health literacy questionnaire were used. To analyze the data using SPSS.22 and Chi-square and Fisher's exact tests, independent t-test, and Pearson's correlation were used. A significant level (0.05) was considered. Results: The average score of health literacy in the intervention group was 70.7 ± 12.12 and in the control group 67.6 ± 15.2 (P = 0.21). The emotional adjustment score was 5.48 ± 2.41 in the intervention group and 7.37 ± 2.41 in the control group (P = 0.0001), and the overall adjustment score was 24.97 ± 4.33 in the intervention group and 3.88 in the control group. ± 27.23 (P = 0.003) that the two studied groups had a statistically significant difference after the educational intervention. The emotional adjustment score in the intervention group (from 6.58 ± 2.63 to 5.48 ± 2.41) and the overall adjustment score from 26.65 ± 4.92 to 24.97 ± 4.33) after the educational intervention significantly significantly improved (P>0.05). A negative and significant correlation was observed between students' emotional adjustment scores and health literacy scores (P=0.018). Conclusion: This study shows that life skills training can effectively improve students' emotional adjustment, but its effect on social and educational adjustment needs further investigation.