Abstract: Based on morphological and molecular phylogenetic methods, a taxonomic revision was conducted on 403 specimens of sisorid catfishes collected from the lower Yarlung Tsangpo River druing 1974, 2019—2023. Detailed examination, combined with historical records, revealed the presence of six genera and ten species of sisorids in the lower Yarlung Tsangpo River, including Glyptosternon maculatum; Glyptothorax cavia, G. cf. gracilis, G. medogensis Chen & He sp. nov., G. rara Chen & He sp. nov.; Pseudecheneis sirenica, Creteuchiloglanis kamengensis; Exostoma tibetanum, E. tenuicaudatum, and Parachiloglanis immaculata Chen & He sp. nov.. The new species G. medogensis was previously misidentified as G. annandalei Hora 1923. It can be distinguished from its congeners in the Yarlung Tsangpo-Brahmaputra basin by the following combination of characters: ventral surface of the simple rays of the paired fins plaited; occipital process separated from anterior nuchal plate element; ventral-fin origin below the vertical from the posterior end of the dorsal-fin base; tip of ventral fin separated from the commencement of the anal fin; slender and shallow caudal peduncle with a depth 6.5%—8.0% SL and a length 18.8%—22.5% SL; and longer head length with 24.1—26.3% SL. The new species G. rara can be distinguished from its congeners in the Yarlung Tsangpo-Brahmaputra basin by the following combination of characters: non-plaited ventral surface of pectoral spine and first pelvic-fin ray; a heart shaped thoracic adhesive apparatus extending anteriorly onto the gular region, posteriorly ending about two thirds the pectoral-fin base; ridges of skin radiate from the posteromedial extent of apparatus forming a slight depressed area and posteriorly open; longer maxillary barbel, extending beyond the end of pectoral-fin base, and reaching the posterior half of pectoral fin; broad pectoral spine, serrated anteriorly with 8 serrae; nasal barbel reaching anterior margin of the eye when adpressed; and a shallow nocth on anterior margin of the lower jaw. The new species Parachiloglanis immaculata was previously misidentified as Parachiloglanis hodgarti. It can be distinguished from its congeners by the following combination of characters: absence of lip fold or post-labial fold; lunate tooth patch on the upper jaw, posterolaterally arched, extending longer laterally than anteroposteriorly, width laterally about twice anteroposteriorly; nearly fused tooth patches on the lower jaw, gap invisible; gill-openings restricted to the sides of the head and extending to about one third the pectoral-fin base; pectoral fin with 16—17 rays; long and low adipose fin, ending with a discrete notch; semilunate caudal fin; presence of a punctate lateral line with small white coloration spots around the lateral-line pores; and absence of conspicuous blotch, spot, or stripe on the body and fins. G. cavia is a new record species in China. Pseudecheneis sirenica was previously misidentified as Pseudecheneis sulcata (McClelland 1842), and its name is revised herein. Morphological characters of each species were described, and a key to the genus and species of the Sisoridae in the lower Yarlung Tsangpo River was provided.