English learning has become a vital educational strategy in many non-English-speaking countries. Vocabulary is a critical element for language learners. Therefore, developing sufficient vocabulary knowledge enables effective communication. However, learning a foreign language is difficult and stressful. In addition, memorizing English vocabulary is often considered boring, and learners may lack motivation for learning activities. To increase English learning motivation and interest, this study constructed a mobile game-based English vocabulary practice system that entails selecting words according to textbook passages, a difficulty ratio, and learning portfolios. The learning activities involved in the system transform vocabulary learning from tedious memorization to game-based learning, thereby enhancing learners' vocabulary memory and their familiarity with curriculum-related vocabulary through various multimedia. An experiment was conducted by dividing students into three groups that involved different vocabulary review methods. All students had similar English proficiency levels, and the course content and instructor were the same for all groups. This study statistically analyzed whether learners become familiar with vocabulary after playing the game. According to the analysis results, students who used the proposed system exhibited higher learning interest, attention, and learning effectiveness, as well as a sense of accomplishment and triumph, compared with other students.