Objectives. This study was aimed at comparing the predictors of health-promoting lifestyle behaviors between smoking and nonsmoking medical students at An-Najah National University located in Palestine. Methods. A descriptive cross-sectional study was performed during the academic year 2017/2018. Medical students were asked to complete a self-reported questionnaire that involved the predictors of Health-Promoting Lifestyle Profile-II. With the use of a suitable available sample composed of a total of 430 medical students, 400 had successfully completed the questionnaire and were included in the study. The data was analyzed by using SPSS version 24 software. Results. The sample included 400 medical students with a mean age of 18.7 years, 311 (77.7%) were females, and 89 (22.3%) were males. The prevalence of smokers in the sample was 110 (27.5%). For the health status of over half the students, 211 (52.8%) were excellent. The total HPLP-II score for smoking students resulted to be significantly lower in comparison to nonsmoking students (131.2 versus 135.7). This significant difference was clear in the interpersonal relation subscale (25.6 versus 26.8) for smoking and nonsmoking students, respectively. The score differences in other subscales were generally lower in smoking students. However, these differences were not consistent with statistical significance. Conclusion. The significant lower total Health-Promoting Lifestyle Profile-II score in smoking students necessitates the urgent need for awareness programs, not only towards smoking but also on how to enhance student health-promoting lifestyle behaviors.