The two-pore domain potassium channel TASK-1 plays an important role in various cell types including neurons and cardiac muscle. The expression of TASK-1 channels at the cell surface is subject to transcriptional and posttranslational regulation. To identify proteins interacting with TASK-1 we performed a split-ubiquitin based yeast two-hybrid screen with a brain cDNA library. One of the interacting proteins found in this way was the endosomal SNARE protein syntaxin-8 (stx8). The interaction was verified by co-immunoprecipitation and GST-pulldown experiments. Expression of TASK-1 in Xenopus oocytes gave rise to an acid-sensitive outward current. The amplitude of this current was reduced to about 25 % when TASK-1 was co-expressed with stx8. An antibody-based luminometric assay showed that co-expression of stx8 also reduced surface expression of TASK-1 to about 25 % of control. Experiments using systematic mutagenesis and construction of chimeras identified a specific interaction of TASK-1 with a region proximal to the SNARE motif of stx8 (aa 100–140). Live-cell imaging of fluorescence-labelled TASK-1 and stx8 in COS-7 and HeLa cells showed some co-localisation at the surface membrane and extensive co-localisation in the early endosomal compartment. Expression of stx8Q179A, a mutant of stx8 which cannot form SNARE complexes, had the same effect on TASK-1 current amplitude as wt stx8 and showed the same co-localisation with TASK-1 in the early endosomal compartment. Mutation of a di-leucine-based endocytosis signal on stx8 diminished the effect of stx8 on TASK-1 current amplitude. Our findings suggest that binding of stx8 to TASK-1 channels promotes endocytosis of the channels.