We report on a new layered semiconductor Tl8Sn10Sb16Se48 with an indirect band gap of 0.45 eV. The novel structure is made of alternating layers of SnSe2-type [Sn5Sb2Se14] and SnSe-type [Tl4Sb6Se10]. The material exhibits two-dimensional (2D) electron variable range hopping at low temperatures, indicating an absence of interlayer coherency of the electronic state. Theoretical calculations unveil a 2D confinement for electrons in the [Sn5Sb2Se14] sheet and confirm the heterostructure nature. This unique electronic structure is attributed to the weak interlayer coupling and structure distortion in the electron-poor [Tl4Sb6Se10] layer that energetically impedes electron propagation.