OBJECTIVE: This study was aimed to investigate the effectiveness of mindfulness-based cognitive therapy (MBCT) on depressive symptoms, brain potential, and neuroimmunoinflammatory factors in patients with depression. METHODS: Sixty-four eligible patients according to the inclusion criteria were randomly divided into the control group and the observation group, with 32 patients in each group. The control group received conventional therapy, while the observation group received MBCT on top of conventional therapy. The depressive symptoms, brain potential, and neuroimmunoinflammatory factors were measured in the two groups. RESULTS: After treatment, the Hamilton Depression Rating Scale score, tumor necrosis factor α, and interleukin-6 levels were decreased, while the World Health Organization Quality of Life Scale score, total number of response execution score, and 5-hydroxy tryptamine level were increased in both groups. Moreover, the Hamilton Depression Rating Scale score, tumor necrosis factor α, and interleukin-6 levels were decreased more significantly, while the World Health Organization Quality of Life Scale score, total number of response execution score, and 5-hydroxy tryptamine level were increased more significantly in the observation group compare to the control group ( P < 0.01). In addition, the latency in the observation group was shorter and the amplitude was longer than those in the control group ( P < 0.01). CONCLUSIONS: Compared with conventional therapy, the use of MBCT combined with conventional therapy can effectively reduce depressive symptoms, suppresses inflammatory responses, and optimize attention and response to target stimulation and is worthy of wide clinical implementation.