Today’s people live in a society with many dangers to their peace and security. The effectiveness of different therapies in psychological variables needs to be evaluated to reach the most precise therapies based on research evidence. This study aimed to compare the effectiveness of existential therapy (ET) and acceptance and commitment therapy (ACT) in alleviating the loneliness and irrational beliefs of male prisoners. In the present quasi-experimental study, the statistical population consisted of all married male prisoners aged between 25 to 45 years in Mashhad Central Prison in the first half of 2017. Among the statistical population, 36 people were selected and then randomly placed in three research groups. The two experimental groups underwent eight separate intervention sessions, ET, and ACT. At the beginning and end of the study, all of the three groups were evaluated by a research questionnaire, including the loneliness scale. The results of data analysis showed that, in comparison with the control group, the changes in the other two groups under ET and ACT were significant as to the feeling of loneliness and irrational beliefs of prisoners. However, there was no significant difference between the effects of these two treatments. The present research was limited in the case of examining the follow-up stage due to lack of access and cooperation of the subjects, incorporating some control variables (such as the history of substance use and psychiatry), and employing other evaluation methods (e.g., interview). It is highly suggested that future research should address these limitations.