This study sought to investigate the underlying mechanisms via which with-nolysine kinases 1 (WNK1) contributed to bone cancer pain (BCP). A rat model of BCP was induced by Walker-256 tumor cell implantation. WNK1 expression and distribution in the lumbar spinal cord dorsal horn and dorsal root ganglion were examined. Findings demonstrate that the WNK1-SPAK/OSR1 signaling contributed to BCP in rats via regulating NKCC1 and KCC2. Suppressing this pathway reduced pain behaviors.