Objective To study the expression of autophagy-related proteins ( Beclin-1, LC3 and p62) in brain tissue with malformations of cortical development and related molecular pathogenesis. Methods The brain tissue of 18 cases with epileptogenic foci resection, including 6 cases of tuberous sclerosis complex (TSC), 6 cases of focal cortical dysplasia type Ⅱb (FCD Ⅱb) and 6 cases of focal cortical dysplasia type Ⅰ ( FCD Ⅰ) , were retrieved.Immunohistochemical study for Beclin-1, LC3 and p62 proteins was performed.The degree of positivity for Beclin-1 and LC3 proteins was compared.Western blot was used to quantitatively analyze the LC3 protein in focal lesion of each disease groups.Results Immunohistochemical study showed that the three proteins were mainly expressed in the dysmorphic neurons and balloon cells/giant cells of TSC and FCD Ⅱb.The positivity was more intense in the dysmorphic neurons than the other cell types.Immunostaining for Beclin-1 showed granular or diffuse cytoplasmic positivity, in addition to the strong expression in axons.On the other hand, LC3 showed diffuse or perinuclear cytoplasmic expression.The staining for p62 was mainly cytoplasmic or perinuclear and sometimes nuclear.In FCD typeⅠ, only individual cells showed positive expression for the three proteins.The number of Beclin-1 and LC3-positive cells was larger in TSC group, followed by FCDⅡb group and FCDⅠgroup.And there were significant differences between TSC group and FCDⅠgroup, as well as FCDⅡb group and FCDⅠgroup (P<0.05).Quantitative expression of LC3 protein by Western blot showed smaller amount in TSC group, followed by FCD Ⅱb group and FCDⅠ group.Conclusions The dysmorphic neurons and balloon cells/giant cells of TSC and FCD Ⅱb show abnormality in autophagy, resulting in intracytoplasmic protein accumulation.There are differences in molecular pathogenesis in these cell types.