As experimentally shown by Hicks and Dresselhaus [16] the value of S is about 2.5 times than that of the bulk through quantum confinement effects by using QW structures. In 2007, Ohta et al. [17] observed a large Seebeck coefficient S = 850 µV K −1 in SrTiO 3 (barrier)/ SrTi 0.8 Nb 0.2 O 3 (well)/SrTiO 3 (barrier) multiple QW (MQW). By analyzing the optical spectra, Choi et al. found that the polaron plays an important role in determining the electronic structure in this MQW. [18] Through orbital reconstruction, recently Geisler et al. [19] also obtained large positive S (≈135 µV K −1 ) in LaNiO 3 /SrTiO 3 MQW at room temperature. As a matter of fact, for oxide or semiconductor MQW structure, the carrier electrons should be confined inside of a thin conducting layer. [16,17] There is valid argument for the attention that this will modified the electronic structure near Fermi level through polaron dimensional effect or quantum confinement effect. [18,20] In addition to high S, another strongly desired characteristic for TE materials is electrical and thermal conductivity, which will allow us to explore the high figures of merit. Venkatasubramanian et al. [21] reported that figure of merit can be further increased by controlling the transport of electrons in Bi 2 Te 3 / Sb 2 Te 3 superlattices. In addition, recently theoretical analyses for WS 2 /WSe 2 suplattices suggest that the ZT values can be enhanced by optimal the thermal conductivity. [22,23] However, for the earlier work of the semiconductor QW structure, the band offset is small and which most likely minimal the anisotropy between in-plane and out-of-plane electrical conductivities. [21,[24][25][26] Under this circumstance, due to the electron tunneling and thermal currents between the layers with these infinite potential barriers heights, the enhancement of the ZT values are rather moderate. On the other hand, for the oxide QW, although the tunneling effect are disappeared, but the thermal conductivity are 1-2 orders of magnitude higher than the semiconductor, [27,28] which limits their application in thermoelectric device.In this paper, we select the PbSe and SnSe as the constituent materials for the MQW structure to enhance Seebeck coefficient and optimal thermoelectric properties. PbSe has excellent thermoelectric properties in the mid-temperature region, along with low lattice thermal conductivity and small forbidden band width (≈0.28 eV). In this heterojunction system, SnSe was chosen as the potential barrier layer because on the one Reduced dimension is one of the effective strategies to modulate thermoelectric properties. In this work, n-type PbSe/SnSe superlattices with quantum-well (QW) structure are fabricated by pulsed laser deposition. Here, it is demonstrated that the PbSe/SnSe multiple QW (MQW) shows a high power factor of ≈25.7 µW cm −1 K −2 at 300 K, four times larger than that of PbSe single layers. In addition, thermal conductivity falls below 0.32 ± 0.06 W m −1 K −1 due to the phonon scattering at interface when the PbSe well thickness...