Objective. A case-control study was adopted to investigate the efficacy and side effects of irinotecan combined with nedaplatin (NP) versus paclitaxel combined with cisplatin for locally advanced cervical cancer (CC) neoadjuvant chemotherapy (NACT) and to analyze the changes in tumor marker levels. Methods. A total of 96 patients with locally advanced CC who were treated from October 2019 to October 2021 were enrolled in our hospital as the research subjects, and their clinical data were collected for retrospective analysis and grouped according to their treatment regimens. Among them, 53 patients received paclitaxel combined with cisplatin as the control group, and the other 43 patients received irinotecan combined with NP as the observation group. The clinical effectiveness of neoadjuvant chemotherapy and alterations in tumor markers (CEA, AFP, CA125, and SCCA) were compared between the two groups. The incidence of common chemotherapy side effects was observed and compared between the two groups, including nausea and vomiting, abdominal pain and diarrhea, liver function impairment, bone marrow suppression, transient hyperglycemia, rash, ECG abnormalities, peripheral neurotoxicity, and muscle aches and pains. Results. The clinical efficiency of neoadjuvant chemotherapy was 97.67% in the observation group and 81.13% in the control group, with no statistically significant difference between the groups ( P > 0.05 ). There was no significant difference in CEA, AFP, and CA125 between the two groups before and after chemotherapy, but the decrease of SCCA before and after chemotherapy was statistically significant. There was no significant difference in the incidence of liver function damage, myelosuppression, abnormal ECG, and rash between the two groups ( P > 0.05 ). There are statistically significant differences in the incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches between the observation and control groups ( P < 0.05 ). The incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches was higher in the control group than in the observation group, with statistically significant differences ( P < 0.05 ). The difference in the incidence of diarrhea and abdominal pain between the observation group and the control group was statistically significant ( P < 0.05 ), and the incidence of diarrhea and abdominal pain in the observation group was higher than that in the control group. Conclusion. Irinotecan in combination with nedaplatin can be an effective neoadjuvant chemotherapy regimen for advanced localized cervical cancer, particularly in patients with combined diabetes.