Collectively, our data demonstrate for the first time the combinational inhibitory effect of ruxolitinib and resminostat in the proliferation and apoptosis of CTCL cell lines and further reveal the importance of AKT, ERK1/2 and JNK signalling as potential targets for CTCL disease management. Here, MAPK3 is linked to primary cutaneous T-cell non-Hodgkin lymphoma.