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Objective: To evaluate the efficacy and safety of resectable locally advanced colorectal cancer (LACRC) after neoadjuvant immunotherapy (IT). Methods: A retrospective analysis of the clinicopathological data of 32 patients with locally advanced colorectal cancer who received neoadjuvant immunotherapy followed by radical surgery at the Cancer Hospital Chinese Academy of Medical Sciences, from January 2019 to February 2024. Fisher's exact test was used for univariate analysis, and Logistic regression model was used for multivariate analysis. Results: Of the 32 patients, 23 were male and 9 were female; the median age was 55 years old. Seven patients with microsatellite instable-high (MSI-H) and 1 patient with microsatellite stable (MSS) received neoadjuvant immunotherapy. Eight patients received neoadjuvant immunotherapy, 16 patients (10 MSI-H and 6 MSS) received neoadjuvant chemotherapy combined with IT, and 8 patients (1 MSI-H and 7 MSS) received neoadjuvant chemoradiotherapy combined with IT. Postoperative pathological results showed that 25 patients achieved pathological complete response (pCR) (78.1%), while 7 patients did not achieve pCR (21.9%). The pCR rates were 94.4% (17/18) in MSI-H patients and 57.1% (8/14) in MSS patients, with statistically significant difference between the two groups (P=0.001). Postoperative complications occurred in 8 patients (25.0%), and there were no secondary operations or perioperative deaths. Multivariate analysis results showed that preoperative carcinoembryonic antigen (CEA) level ≥5 ng/ml(OR=0.035,95% CI:0.003～0.260, P=0.003), MSI-H and MSS POLE positive（OR=19.000，95% CI：2.573～399.227，P=0.012）were related to pCR. Conclusions: Neoadjuvant immunotherapy is safe and effective for resectable LACRC. Neoadjuvant immunotherapy alone for resectable MSI-H colorectal cancer (CRC) can achieve satisfactory results, and neoadjuvant immunotherapy in combination with various forms of conventional therapy for patients with resectable MSS CRC could also achieve better short-term effects.