Online learning (e-learning) is one of new breakthroughs in world of education in Indonesia. Regarding the level effectiveness of using e-learning systems for students' understanding is still at a sufficient level. A sufficient level of understanding can occur due to low interpretation and extrapolation abilities in students. The purpose in this study is to determined relationship between effectiveness of online-based learning (e-learning) on student understanding at Muhammadiyah University of Yogyakarta. The research design used in this study is quantitative with cross sectional approach using Pearson product moment correlation test. The results of the study stated that the effectiveness of online-based learning in UMY Nursing students was effective 85.8% of the total 288 respondents. The level of students’ understanding is in sufficient category, evidenced by 41.7% of students stating their level of understanding in a sufficient range. The conclusion of the study states that level effectiveness of learning methods using E-Learning has a significant relationship to the level of understanding on students, as evidenced by the p value = 0,000 (<0.005). Suggestions in this research are for using of an internet connection that is more maximized again to optimize the learning process, so that it can improve the understanding.