ABSTRACT: Some esophageal cancer patients complicated with depression exhibit cognitive impairments. Frontal electroencephalogram (EEG) may be used as a reliable biomarker for prefrontal-mediated cognitive functions. This study was to investigate alterations of EEG and frontal cognitive impairment in esophageal cancer patients complicated with depression and to assess their correlation.Sixty-five esophageal cancer patients with depression (study group) and 62 healthy controls (control group) were included in this study. The study group were assigned into psychotic depressed (PD, n = 32) and nonpsychotic depressed (NPD, n = 33) subgroups based on complication with psychotic symptoms (Brief Psychiatric Rating Scale [BPRS] >35). EEG examination, Beck self-rating depression scale, and BPRS were used to assess clinical symptoms. Chi-square test, two independent sample t-test, one-way analysis of variance, and Kruskal-Wallis test were utilized to compare the variables between two groups. EEG abnormalities and scores of frontal cognitive function test were analyzed by partial correlation analysis in the PD and NPD subgroups.Compared with control group, the study group displayed greater scores either in the Stroop test (19.89 ± 2.05 vs. 24.12 ± 2.19, P = 0.006) or Color Trails Test (CTT; 11.92 ± 1.01 vs. 15.02 ± 1.63, P = 0.008), and reduced score (35.05 ± 2.01 vs. 32.11 ± 2.38, P = 0.007) in the verbal fluency test (VFT). Compared to NPD subgroup, PD subgroup exhibited increased scores in Stroop test (22.89 ± 2.07 vs. 25.38 ± 2.32, P = 0.009) and CTT (13.16 ± 1.71 vs. 15.82 ± 1.13, P = 0.008). Moreover, increased scores in Stroop test and CTT as well as scores in VFT were associated with the severity of depression. The study group had an abnormal frontal EEG, such as α forward, α asymmetry, α moderation, and increased θ activity relative to control group. Similarly, compared with NPD subgroup, PD subgroup displayed α forward, α asymmetry, and α moderation. The correlation test revealed that α forward and α asymmetry were negatively associated with VFT score, but positively correlated with the scores of CTT and the Stroop test in PD subgroup. In addition, α asymmetry in NPD subgroup was positively related to CTT scores.This study indicated that frontal cognitive impairment in esophageal cancer patients complicated with depression is associated with EEG alterations.