Constitutively active MKK3, MKK6, p38γ and p38δ induced phosphorylation of Hsp27 at Ser78 and Ser82 in a MK2-dependent manner in NSCLC cells with low p38 activity, while dominant negative MKK6A mutant and knockdown of p38γ and p38δ in cells with high p38 activity abrogated phosphorylation of Hsp27 on these sites. Here, MAP2K6 is linked to non-small cell lung carcinoma.