The recently discovered Weilasituo Sn-polymetal deposit is located in the southern part of the Great Xing'an Range of Inner Mongolia, NE China, which is belonged to the eastern part of the Central Asian Orogenic Belt (CAOB). Sn-polymetal mineralization is closely related to the emplacement of the Early Cretaceous fine- to medium-grained quartz porphyry. Three types of mineralization have been recognized at Weilasituo with the disseminated and stockwork Sn-polymetal mineralization mainly hosted by the quartz porphyry, the vein-type Sn-polymetal mineralization hosted by NE-trending and WE-trending fractures and faults in the upper and outer part of the porphyry, and breccia mineralization occurred within a steep cryptoexplosive breccia pipe. The ore-related alteration typically consists of Na-Ca-Sr alteration and greisen. In order to understand the petrogenetic link between the Sn-polymetal mineralization and the host quartz porphyry, this paper presents new whole-rock geochemistry for the quartz porphyry, EPMA analysis of ore and gangue minerals, and in situ U-Pb dating of cassiterite. The Laser Abrasion Multiple Collector Inductively Coupled Plasma Mass Spectrometer (LA-MCICP-MS) cassiterite U-Pb dating yields two well-defined isochron ages of 138 ± 6 Ma for disseminated ore and 135 ± 6 Ma for the vein-type ore, which could be regarded as the ore-forming age. The cassiterite U-Pb ages (ca. 138–135 Ma) determined in this study, together with previous data, reveals the close temporal and genetic relationship between the mineralization event and the emplacement of the quartz porphyry. The quartz porphyry is characterized by high SiO2, Na2O, and A/CNK values (1.09–1.21). REE tetrad effect combined with extremely high Rb/Sr, K/Ba ratios and low K/Rb, Zr/Hf, La/Nb, La/Ta and Eu/Eu* ratios indicate that the quartz porphyry is a highly fractionated peraluminous I-type granite that is hydrothermally altered. Low εNd(t) values of 4.27–0.28 and the two-stage depleted mantle Nd model ages (T2DM = ca. 1279–908 Ma) for the quartz porphyry, are similar to granites in Precambrian microcontinents of the eastern part of the Central Asian Orogen (CAOB). This suggests that the quartz porphyry was derived from the remelting of juvenile crust and Precambrian rocks in an extensional setting. Therefore, the highly fractional crystallization and magmatic-hydrothermal interactions of the quartz porphyry have contributed to the formation of the Weilasituo Sn-polymetal deposit.