A new wave of treatments has emerged to target the altered nervous system and maladaptive conceptualizations about pain for chronic low back pain. The acceptability of these treatments is still uncertain. We conducted a qualitative study alongside a randomized controlled trial to identify perceptions of facilitators/barriers to participation in a non-pharmacological intervention that resulted in clinically meaningful reductions across 12 months for disability compared to a sham intervention. We conducted semi-structured interviews with participants from the trial's active arm after they completed the 12-week program. We included a purposeful sample (baseline and clinical characteristics) (n=20). We used reflexive thematic analysis informed by the Theoretical Framework of Acceptability for health care interventions. We identified positive and negative emotional/cognitive responses associated with treatment acceptability and potential efficacy, including emotional support, cognitive empowerment, readiness for self-management, and acceptance of face-to-face and online components designed to target the brain. These findings suggest the importance of psychoeducation and behaviour change techniques to create a positive attitude towards movement and increase the perception of pain control; systematic approaches to monitor and target misconceptions about the interventions during treatment; and psychoeducation and behaviour change techniques to maintain the improvements after the cessation of formal care. Perspective: This article presents the experiences of people with chronic low back pain toward a new non-pharmacological brain-targeted treatment that includes face-to-face and self-directed approaches. The facilitators and barriers of the interventions could potentially inform adaptations and optimization of treatments designed to target the brain to treat chronic low back pain.