The study aimed at investigating the influence of E-learning Self-Efficacy (ELSE) on the acceptance of e-learning by using the Technology Acceptance Model (TAM). According to the TAM which used as the theoretical basis, both of the Perceived Usefulness (PU) and the Perceived Ease of Use (PEOU) influence directly the end user's Behavioral Intention (BI) to accept a technology. A survey was used to collect information about the perceptions of Al-Aqsa university students. Collected data was analyzed using the regression equation by SPSS. A structured questionnaire was used to obtain responses from (592) students who took the e-courses of the "instructional technology, research methods, measurement and evaluation". The most significant results of the study showed that Al-Aqsa university students have high levels of acceptance and Self Efficacy toward E-Learning representing a rate above 75%. Furthermore, there are positive and significant relationships between dependence and independence variables. However, the study found a significant relationship between finding ELSE, PEOU, PU and BI (Y= 1.2 + 0.05ELSE + 0.06PEOU + 0.16PU + e, r = 0.65, P<0.01). Other relationships were found among variables such as ELSE, PEOU and PU (Y = 7.5 + 0.11ELSE + 0.21PEOU + e, r = 0.62, P<0.01), ELSE and PEOU (Y = 0.56 + 0.242ELSE +e, r = 0.64, P<0.01).