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The process skill based interactive instructional multimedia was developed to teach students in learning Scince independently with the content, exercise, virtual laboratory and evaluation connected to the process skill. This study aims to produce a process skill based interactive multimedia which is properly used in learning Science and to know the increase in the learning outcome of students from the use of process skill based interactive multimedia in Science. This study belongs to a research and development which uses the R&D model by Borg and Gall and combined with the instructional design model by Dick and Carey. The result of the validation and trial process shows that the developed interactive instructional multimedia is in the criteria of very decent. This result indicates that the multimedia is proper to use in learning Science. The result of hypothesis testing indicates that there is a difference between the learning outcome students in Science that use a process skill based interactive multimedia and the learning outcome students in Science that use a presentation media powerpoint. Therefore, the process skill based interactive instructional multimedia is proper and effective used in learning Science.