Cognitive defusion may enhance healthy coping with negative self-referential thoughts amongst college students. However, research is needed to examine how to effectively introduce and teach defusion to this population. The current pilot study tested the usability of and satisfaction with the D-FUSE program, a single-session, web-based program for a mixed sample of undergraduates and its effectiveness in producing improvements in cognitive defusion and self-criticism. In an undergraduate sample (N = 141), the D-FUSE program was found to be usable and satisfactory. Program engagement rendered significant reductions in the believability of and emotional discomfort produced by negative self-referential thoughts. Further improvements to program development and administration are considered.