Objective To analyze the correlation between serum nerve growth factor (NGF) level and the effect of electroconvulsive therapy (ECT) in patients with treatment-resistant depression (TRD). Methods Sixty patients with TRD (TRD group) in the 987th Hospital of PLA Joint Logistics Support Force from February 2020 to December 2021 were enrolled, and 60 healthy volunteers in the same period were selected as control group. All patients with TRD received ECT treatment with ketamine alone for 8 times. Serum NGF level was detected by enzyme-linked immunosorbent assay (ELISA). Hamilton Depression Rating Scale (HAMD-17) and Brief Psychiatric Rating Scale (BPRS) were used to evaluate the severity of illness. Results The baseline serum NGF level in TRD group was significantly lower than that in the control group (P＜0.001). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) of baseline serum NGF level in diagnosing TRD was 0.953. The remission rate of antidepressant was 76.7% (46/60). With ECT treatment, serum NGF level increased (P＜0.001). The serum NGF level of TRD patients in the remission group was always higher than that in the non-remission group (P＜0.001). The increase trend of serum NGF level in TRD patients in the remission group was significantly higher than that in non-remission group (P=0.001). The changes of serum NGF level were negatively correlated with the changes of HAMD-17 score and BPRS score P＜0.05). The AUC of baseline serum NGF level in predicting non-remission of ECT treatment in TRD patients was 0.750. Baseline serum NGF level＞7.97 pg/ml was still an independent risk factor affecting the remission outcome of ECT in TRD patients (P=0.015). Conclusions During ECT treatment, the serum NGF level of TRD patients gradually increases with the improvement of the disease, and the baseline serum NGF level can be used as a biomarker to predict the remission of TRD patients after ECT treatment.