MCT-1 (multiple copies in T-cell lymphoma-1), a novel oncogene, was originally identified in T-cell lymphoma. A recent study has demonstrated that MCT-1 is highly expressed in 85% of diffuse large B-cell lymphomas (DLBCL). PKC (protein kinase C) plays an essential role in signal transduction for multiple biologically active substances for activating cellular functions and proliferation. In this study, we found that the mRNA and protein expression levels of MCT-1 were visibly decreased after knocking down PKC by siRNA in SUDHL-4 and OCI-LY8 DLBCL cell lines. A selective PKC inhibitor, sotrastaurin, effectively inhibited cell proliferation and induced cell apoptosis in a dose- and time-dependent manner. Meanwhile, we also observed that the cell cycle was arrested in the G1 phase in sotrastaurin-treated cells. In addition, MCT-1 was down-regulated in the sotrastaurin treatment group in vivo. Furthermore, we demonstrated that the PKC inhibitor sotrastaurin induced cell apoptosis and cell cycle arrest in DLBCL cells potentially through regulating the expression of MCT-1. Our data suggest that targeting PKC may be a potential therapeutic approach for lymphomas and related malignancies that exhibit high levels of MCT-1 protein.