This study aimed to investigate the effect of a patient education and rehabilitation program (PERP) on anxiety, depression, and quality of life in muscle invasive bladder cancer (MIBC) patients underwent adjuvant chemotherapy.One hundred and thirty MIBC patients about to receive adjuvant chemotherapy with 4-cycle gemcitabine and cisplatin (GC) regimen (16 weeks) were consecutively enrolled and randomly allocated into PERP group and control group as 1:1 ratio. Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores and Quality of Life Questionnaire (QLQ-C30) scores were assessed before treatment (W0) and after treatment (W16).After 16-week treatment, PERP group exhibited decreased HADS anxiety score (P = .036), ΔHADS anxiety score (W16-W0) (P < .001) and percentage of anxiety patients (P = .019) compared to control group. And PERP group presented with numerically reduced HADS depression score but without statistical significance (P = .076) compared to control group, while lower ΔHADS depression score (W16-W0) (P = .014) and percentage of depression patients (P = .015) compared to control group. As to quality of life, QLQ-C30 global health status score (P = .032), Δglobal health status score (W16-W0) (P = .003) and Δfunctional score (W16-W0) (P = .005) were higher in PERP group compared to control group. However, no difference of QLQ-C30 functional score (P = .103), QLQ-C30 symptom score (P = .808) or Δsymptom score (W16-W0) (P = .680) was observed between two groups.PERP relieves anxiety, depression and improves quality of life in MIBC patients underwent adjuvant chemotherapy.