【Objective】 To explore the safety and efficacy of neoadjuvant chemotherapy (NAC) combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection (RC-PLND) for muscle-invasive bladder cancer (MIBC). 【Methods】 The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed, including 71 patients (70.3%) who received NAC (NAC group) and 30 (29.7%) who received NAC combined with immunotherapy (NAC combine immunotherapy group). The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response (pCR) and pathological partial response (pPR). 【Results】 There were no significant differences in the baseline data between the two groups (P>0.05).However, the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group (69.0% vs. 46.7%, P=0.034).Compared with NAC group, NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR (60.6% vs. 83.3%, P=0.026; 45.1% vs. 70.0%, P=0.022).Furthermore, the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC, but the difference was not significant (53.3% vs. 33.8%, P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR (P<0.05).In addition, the most common adverse events during neoadjuvant therapy were anemia, decreased white blood cells, nausea, and vomiting, but most of them were grade 1—2 and could be relieved through symptomatic treatment. 【Conclusion】 NAC combined with immunotherapy is safe and effective, which can improve the rate of pathological downstaging, pPR and pCR, without increasing the incidence of adverse reactions.