E-cigarette use is a growing public health concern, especially because of the potential health risks it poses. This study focuses on assessing e-cigarette dependence and the factors associated with it among Palestinian young adults. A cross-sectional survey was conducted from January to May 2023 among university students in the West Bank. A self-administered questionnaire was used to collect demographic data, knowledge, and attitudes regarding e-cigarettes. E-cigarette dependence was assessed using the Penn State Electronic Cigarette Dependence Index. The study included 386 university students who used e-cigarettes. Many of them started using e-cigarettes at a young age, and 54.7% were dual users of e-cigarettes and traditional tobacco. High levels of dependence were reported in 11.4% of participants, and moderate dependence in 28.8%. Several factors were identified through multivariate linear regression as significantly associated with e-cigarette dependence: a higher monthly allowance (β = 0.116, 95% CI: 0.128- 1.124,
p
= .014), having a father who uses tobacco (β = 0.095, 95% CI: 0.030- 1.638,
p
= .042), having a close friend who smokes traditional cigarettes (β = 0.095, 95% CI: 0.019- 1.667,
p
= .045), using e-cigarettes in areas where traditional smoking is prohibited (β = 0.175, 95% CI: 0.689–2.330,
p
< .001), using e-cigarettes to quit other forms of tobacco (β = 0.134, 95% CI: 0.434–2.314,
p
= .004), and a more negative attitude score (β = − 0.210, 95% CI: − 0.285- − 0.112,
p
< .001). The study revealed high levels of e-cigarettes dependence among the participants among young adults, with associated variables such as monthly allowance, attitudes, and age of e-cigarette initiation. Policymakers, educators, and healthcare professionals should collaborate to address e-cigarette dependence among young adults, taking into consideration social, environmental, and socioeconomic factors.