The purpose of the study was to examine the effects of gender differences on the application of CALL programs for second language acquisition. Gender difference is an important theme in linguistic education because it influences the design of curriculum, teaching method, instructional strategy, and students' learning processes. This study applied a mixed-methods design, using both quantitative and qualitative methods, both descriptive and comparative in design. The participants were 200 students (male=34, Female=166) taking EFL courses and CALL programs in Wenzao Ursuline College of Languages in Taiwan. Findings from the study indicated that although 94% students (N=188) acknowledge that learning English with CALL programs can increase the efficacy of English learning, more 57.2% female students (N=95) than 11.7% male students (N=4) felt that learning English with computer is difficult because it requires the basic computer knowledge.