Students' science process skills are still less than optimal because learning tends to be monotonous and oriented towards the final result. This study aims to analyze the determination of project-based E-LKPD with ethnoscience on students' science process skills and to examine the mediating role of digital literacy and learning independence. The approach used is descriptive quantitative. The study population was all students of SMA Negeri 2 Padang Sidimpuan (approximately 35 people), with a sample of 12 students taken using a purposive sampling technique. Data collection was carried out through a process skills questionnaire after learning using project-based E-LKPD integrated with local wisdom. Data analysis used descriptive analysis by calculating the average, percentage, and standard deviation. The results showed that the project-based E-LKPD with ethnoscience obtained an effectiveness percentage of 90.83% (very good category). All aspects assessed, including ease of use (92.7%), relevance of local wisdom (93.3%), observation skills (85.6%), asking and formulating problems (86.7%), designing and conducting projects (90.0%), analyzing and concluding (89.4%), communicating (93.9%), and overall effectiveness (92.1%) were in the very good category. Thus, the E-LKPD ethnoscience was proven effective in improving students' science process skills, with digital literacy and learning independence acting as mediating variables.