The aim of this study was to compare the effect of cognitive behavioral intervention (CBI) combined with the resilience model (CBI + R) vs CBI alone on depression symptoms, anxiety symptoms, and quality of life of end-stage renal disease (ESRD) patients undergoing hemodialysis replacement therapy. Method: Fifty-three subjects were randomly assigned to one of two treatment groups. The control group (n= 25) was provided with treatment strategies based on a cognitive behavioral approach, while the experimental group (n= 28) were given the same techniques plus resilience model strategies. Five psychological instruments were applied: Beck Depression Inventory, Beck Anxiety Inventory, Mexican Resilience Scale, cognitive distortions scale, and the Kidney Disease related Quality of Life questionnaire. Participants were assessed at baseline (before treatment), eight weeks later (end of treatment), and four weeks after the end of treatment (follow up). The results were analyzed by ANOVA for repeated measures with a Bonferroni-adjusted test method, withp< 0.05 considered significant. Results: The experimental group had significant differences in total and somatic depression as well as differences in the dimensions of cognitive distortions and a significant increase in the dimensions of resilience. The control group had significant differences in all variables but showed lower scores in the evaluated times. Conclusions: The resilience model strengthens and enhances the effectiveness of the cognitive behavioral approach to reduce symptoms of depression and anxiety in patients with ESRD.