Given the unique stresses inherent in raising a child with autism, mothers may find it challenging to maintain a positive sense of self-efficacy. This study sought to determine the effects of Acceptance and Commitment Therapy (ACT) on self-efficacy of mothers of children with autism. This quasi-experimental research had a pretest-posttest control group design. The statistical population of the study included mothers of children with autism in Isfahan from among whom 30 individuals were selected via convenience sampling and were randomly assigned to experimental (N=15) and control (N=15) groups. Due to subject attrition, the sample size reduced to 10 and 12 in the experimental and control groups, respectively. The data were collected by Berkeley Parenting Self-Efficacy Scale- Second Grade Version (Holloway et al., 2005). The experimental group received eight 90-minute sessions of ACT, while the control group received no intervention. The data were analyzed by multivariate analysis of covariance (MANCOVA). The results showed that ACT was effective in increasing self-efficacy and its components (responsibility,  self-management, accepting child as an individual, and positive evaluation about child) among mothers of children with autism (p<0.05). Findings suggest that ACT can be effective in promoting self-efficacy of mothers of children with autism and may have promise in helping mothers better adjust to the difficulties in raising such children.