Parotocinclus kwarup, new species, is described as a new hypoptopomatine cascudinho from tributaries of the upper Xingu River in the Amazon basin of Brazil. The new species is distinguished from its congeners in northeastern and southeastern Brazil by having the cheek canal plate elongated posteriorly on the ventral surface of the head and in contact with the cleithrum. Parotocinclus kwarup, new species, is diagnosed from other species of Parotocinclus in the Amazon, Orinoco, and Guianas watersheds by the number of oral teeth, the snout length, having odontodes on the ventral surface of the first pelvic-fin ray bent and pointing mesially, lacking a Y-shaped light marking dorsally on the head (from the posterodorsal margin of orbit to posterior parieto-supraoccipital tip), lacking premaxillary and dentary accessory teeth, and having an adipose fin. The extinction risk of the new species is preliminarily assessed as Least Concern based on its wide distribution area and its inferred presence in the large Xingu Indigenous Park.