Game-based learning supported by mobile intelligence technology has promoted the renewal of teaching and learning models. Herein, a model of Question-Observation-Doing-Explanation (QODE) based on smart phones was constructed and applied to science learning during school disruption in COVID-19 pandemic. In this study, from the theoretical perspective of cognitive-affective theory of learning with media, Bandura’s motivation theory and community of inquiry model, self-report measure was used to verify the effect of students’ scientific self-efficacy and cognitive anxiety on science engagement. A total of 357 valid questionnaires were used for structural equation model research. The results indicated that two types of scientific self-efficacy, as indicated by scientific learning ability and scientific learning behavior, were negatively associated with cognitive anxiety. In addition, cognitive anxiety was also negatively correlated to four types of science engagement, as indicated by cognitive engagement, emotional engagement, behavioral engagement, and social engagement through smartphone interactions. These findings provide further evidence for game-based learning promoted by smart phones, contributing to a deeper understanding of the associations between scientific self-efficacy, cognitive anxiety, and science engagement. This study points out that the QODE model is suitable for implementing smart mobile devices to students’ science learning.