Self-explanation (SE) is an effective strategy for improving understanding and it relied on learners’ proper deployment of prior knowledge. Surprisingly, there is limited research on how might misconceptions affects learning despite they are inherent part of learners’ knowledge system. We examine the influence of SE on processes and outcomes of science learning for 36 sixth grade students by varying degrees of prior knowledge and relevant misconceptions. The SE group read and self-explained a text describing state changes of water requiring proper notions of molecules while the control group read twice and think aloud. The results indicated that there are no effects of SE, prior knowledge for learning outcomes. However there is significant effect of SE by misconception interaction. Low misconception students benefit from SE but not for high misconception counterparts. SE did influence amounts and types of verbal protocol students generated. The results indicated that the influence of SE heavily modulated by learners’ misconceptions.