The purpose of this study was to examine the association between teacher-child interaction and preschoolers’ engagement, and to explore the role of gender in this association. One hundred and thirtyfive preschoolers and their classroom teachers in East Tennessee of the U.S. participated in this study. The parents provided children’s demographic information, and classroom teachers completed the questionnaires on preschoolers’ engagement and the quality of teachers’ interaction with each child. The results showed that boys had lower levels of classroom engagement, and a lower quality of interactions with teachers compared to girls. Hierarchical regression analysis revealed that the quality of teachers’ interactions with girls largely accounted for the gender differences in preschoolers’ engagement levels. However, the gender as a moderator between teacher-child one-on-one interaction and preschoolers’ engagement was not found. Compared to other confounders, preschoolers whose mothers having higher educational degrees were more likely to be engaged in the classroom activities.