Resilience factors have been suggested as key mechanisms in the relation between symptoms and disability among individuals with chronic pain. However, there is a need to better operationalize resilience and to empirically evaluate its role and function. The present study examined psychological flexibility as a resilience factor in relation to symptoms and functioning among 252 adults with chronic pain applying for participation in a digital ACT-based self-help treatment. Participants completed measures of symptoms (pain intensity, and anxiety), functioning (pain interference and depression), as well as the hypothesized resilience factor psychological flexibility (measured as avoidance, value obstruction, and value progress). As expected, symptoms, functioning and resilience factors were significantly associated. Hierarchical linear regression analyses showed that psychological flexibility significantly contributed to the prediction of pain interference and depression when adjusting for age, pain and anxiety. Also, participants with low levels of psychological flexibility were more likely to be on sick leave. Furthermore, a series of multiple mediation analyses showed that psychological flexibility had a significant indirect effect on the relationship between symptoms and functioning. Avoidance was consistently shown to contribute to the indirect effect. Results support previous findings and suggest the importance of psychological flexibility as a resilience factor among individuals with chronic pain and anxiety.