Integrin linked kinase (ILK) is an essential transducer of integrin and growth factor signals, and its protein levels and activity are often elevated in solid tumours. ILK physically links integrins and receptor tyrosine kinases to the actin cytoskeleton, and genetic or pharmacologic inhibition of ILK activity blocks cell migration, making it an attractive target for development of anti-cancer therapeutics. Many of the functions of ILK rely on its protein adaptor role to regulate various oncogenic signals. In this study we found that levels of activated p38β, the predominant p38 isoform in bladder cancer cells, directly correlated with the migratory capacity of bladder cancer cells. RNAi knockdown of either p38β or ILK markedly inhibited migration of cells toward serum. Consistent with this, depletion of either ILK or p38β in bladder cancer cell lines resulted in disruption of the actin cytoskeleton. However, p38 knockdown did not affect cellular ILK levels, suggesting that p38 is an effector of ILK-dependent migration in these cells. Using co-immunoprecipitation, proximity ligation and bimolecular fluorescent complementation assays, we found that ILK selectively forms complexes with p38β, indicating that interaction with ILK plays a critical role in stabilizing p38β in these cells. Treatment of ILK-depleted cells with the 26S proteosomal inhibitor MG132 partially rescued p38 levels, suggesting a key role for ILK is the protection of p38b from proteosomal degradation. Interestingly, a canonical target of ILK signalling, Akt Ser473 phosphorylation, was not affected by ILK depletion in these experiments. These results identify a novel ILK-p38β axis that plays important role in cancer cell migration. Thus targeting the ILK-p38 pathway is a potential strategy to inhibit cancer metastasis.