Objective Present study aimed to characterize the alteration of cortical thickness in first-episode, never-medicated, adult patients with major depressive disorder (MDD), and explore whether such deficits were related with their disease duration and clinical symptom severity. Methods Thirty-seven adult MDD patients were recruited from March 2013 to August 2015 as patient group, and 41 healthy volunteers were as control group. All the patients underwent three-dimensional spoiled gradient recalled (3D-SPGR) sequences, and the images were acquired. Constructions of the cortical surface were developed from 3D-SPGR images using FreeSurfer software, and the thickness of the entire cortex was measured according to the automated surface reconstruction, transformation, and high-resolution inter-subject alignment procedures. Finally, cortical thickness was compared between the two groups, and the relativity between clinical symptom severity, disease progression and clinical scores were analyzed using the General Linear Model (GLM). Results Our results revealed a significant increase in cortical thickness(P<0.05, false discovery rate corrected) in the left anterior and middle cingulate cortex, bilateral precentral cortex, left paracentral cortex, bilateral superior parietal cortex, left temporal pole, and right lateral occipital cortex (cortical thickness 1.89-2.87 mm, cortical volume 34-384 mm2, P<0.05) in MDD patients compared to healthy controls, while no reversed alternation was found. In addition, clinical symptom severity and disease progression showed no correlation with the cortical thickness abnormalities in MDD group(P>0.05). Conclusion Excluding the impact of treatment, our study showed that the cortical thickness change was mainly located in the prefrontal-limbic system in the in early course of MDD.