Objective To investigate the correlation and possible mechanisms between estrogen levels and the occurrence of neuropathic pain caused by paclitaxel chemotherapy. Methods A total of 113 postoperative cervical cancer patients aged 65 to 75 years old were selected for adjuvant chemotherapy with paclitaxel. The patients suffer from tumors staged Ⅰ or Ⅱ according to the International Federation of Gynecology and Obstetrics (FIGO) clinical staging system. Two hours after the completion of chemotherapy, the presence of neuropathic pain in patients was assessed using the DN4 Neuropathic Pain Assessment Questionnaire (DN4), and based on the DN4 test results, patients were divided into two groups: the neuropathic pain group (NP group, n=69) and the non‑neuropathic pain group (Non‑NP group, n=44). The levels of estrogen in the blood before chemotherapy (empty stomach on the morning of the first day) and after chemotherapy (two hours after the completion of chemotherapy) were detected using the enzyme‑linked immunosorbent assay, the hematology analyzer detects the absolute values of neutrophils and lymphocytes, while the neutrophil/lymphocyte ratio (NLR) was calculated. Pearson correlation analysis was used to investigate the correlation between estrogen levels and the occurrence of paclitaxel‑induced neuropathic pain while the multifactorial unconditional logistic regression analysis was used to screen for factors that may be associated with the occurrence of neuropathic pain. In addition, the application of the receiver operating characteristic curve (ROC curve) was used to analyze the predictive value of estrogen for the occurrence of paclitaxel‑induced neuropathic pain. Results The prevalence of diabetes mellitus and NLR after chemotherapy in the NP group were higher than that in the non‑NP group (all P<0.05), in contrast, the estrogen level in the NP group was lower than that in the non‑NP group (P<0.05). NLR after chemotherapy was higher than that before chemotherapy in both groups (all P<0.05). The results of Pearson correlation analysis showed that the Spearman correlation coefficient was −0.354 (P<0.001) when the two variables (estrogen levels and the occurrence of paclitaxel‑induced neuropathic pain) had a two‑sided confidence of 0.01. The two variables had a certain correlation and a negative correlation. Multivariate unconditional logistic regression analysis showed that estrogen level before chemotherapy was associated with neuropathic pain after paclitaxel chemotherapy [odds ratio (OR) 0.818 (95% confidence interval (CI) 0.732, 0.915), P<0.001]. The area under the ROC curve was 0.709, while the optimal diagnostic cut‑off point was 36.55. The correct diagnostic index was 0.405 [(95% CI 0.608, 0.811), P<0.001]. There was no significant difference in other indexes (P>0.05). Conclusion Estrogen may reduce the incidence of neuropathic pain from paclitaxel chemotherapy by suppressing the inflammatory response in patients.