Photomorphogenesis is an important process in which seedlings emerge from soil and begin autotrophic growth. Photomorphogenesis mechanisms include light signal perception, signal transduction, and the modulation of light-responsive genes expression, ultimately leading to cellular and developmental changes. Phytochrome-interacting factors (PIFs) play pivotal roles in negatively regulating photomorphogenesis. Light-induced activation of phytochromes triggers the rapid phosphorylation and degradation of PIFs, but the kinases responsible for the phosphorylation of PIFs are largely unknown. Here, we show that Arabidopsis MPK6 is a kinase involved in phosphorylating PIF3 and regulating red (R) light-induced cotyledon opening, a crucial process during seedling photomorphogenesis. MPK6 was activated by R light, and cotyledon opening angle in R light was reduced in mpk6 seedlings. MKK10, a MAPKK whose function is currently unclear, appears to act as a kinase upstream of MPK6 in regulating cotyledon opening. The activation of MPK6 by MKK10 led to the phosphorylation of PIF3 and accelerated its turnover in transgenic seedlings. Accordingly, the overexpression of PIF3 suppressed the MKK10-induced cotyledon opening. MKK10-MPK6 function downstream of phyB in regulating seedlings cotyledon opening in R light. Therefore, MKK10-MPK6 cascade appears to mediate the regulation of R light-controlled seedling photomorphogenesis,via a mechanism that might involve the phosphorylation of PIF3.