Speaking has been widely thought as the most effective way for students to learn and communicate English as a foreign language. However, this oral skill is a challenging task to university students. This study therefore focuses on the difficulties encountered by non-English majored freshmen while learning speaking English as a foreign language at a university in the Mekong Delta region. The study also explores whether there are any statistically significant differences from the variable of gender of the students. It was a descriptive study using questionnaire. The quantitative data from the questionnaire were undertaken with 103 freshmen at a university. The findings indicated students’ difficulties while learning speaking English were associated with linguistic and instructor domains. Implications for further practices are discussed.