Science performance is highly affected by students’ reading comprehension. Recently, there has been a growing attention to the role of linguistic features for science performance, but findings are ambivalent, especially when looking into item word count. The aim of this study was to investigate the interaction of students’ reading comprehension and item word count of given science measures on performance, controlling for students’ cognitive abilities, gender, family language, and school track. The sample consisted of N = 2051 German students in grades 10 and 11. Students completed (scientific) literacy measures. We then applied a multilevel logistic regression to investigate the hypothesized interaction effect of reading comprehension and word count on students’ science performance. The results showed a significant interaction of students’ reading comprehension and word count on science performance, controlling for several covariates. Particularly students with high reading comprehension benefit from science items with increasing word count. Our findings empirically support previous research, showing that reading comprehension is crucial for science performance and enhances the interaction between reading comprehension and linguistic features of written text in science subjects. Finally, theoretical and practical implications and limitations of this study are discussed.