Abstract: Objective To investigate the effects of CD5 on the chemotherapy sensitivity of Jeko-1 mantle cell lymphoma cell line and underlying mechanisms. Methods CD5 gene in Jeko-1 (P) cells was knocked out by Crispr/cas9 method, obtaining CD5 negative Jeko-1(N) cells. Then, the expression of CD5-E1A and CD5-E1B were measured by RT-PCR and ELISA using Jeko-1(P) and Jeko-1(N) cells. The inhibitory effects of daunorubicin and vincristine on the proliferation of Jeko-1(P) and Jeko-1(N) cells were examined by MTS assay. The levels of IL-10 in Jeko-1(P) and Jeko-1(N) cells were determined by ELISA. The levels of NF-κB signaling pathway related proteins p-IKKβ, p-IκB and p-p65 in Jeko-1(P) and Jeko-1(N) cells with or without exposure to BAY 11-7082 were measured by Western blotting. The levels of IL-10 in Jeko-1(P) and Jeko-1(N) cells with or without exposure to BAY11-7082 were determined by ELISA. Results The expression of CD5-E1A and CD5-E1B were determined in Jeko-1(P) cells rather than Jeko-1(N) cells, with reduced secretion of IL-10 (P<0.05). Compared with Jeko-1(P) cells, Jeko-1(N) cells showed an increased proliferation inhibitory rate after 24 and 48 h of exposure to daunorubicin and vincristine (P<0.05). No significant difference was found as to the levels of p-IKKβ, p-IκB, p-p65 (inside and outside the nucleus) and IL-10 between Jeko-1(N) and Jeko-1(P) cells after- treated with BAY 11-7082 (P>0.05). Compared with Jeko-1(P) cells without exposed to BAY 11-7082, Jeko-1(P) and Jeko-1(N) after exposure to BAY 11-7082 produced remarkably reduced levels of p-IKKβ, p-IκB, p-p65 (inside and outside nucleus) and IL-10 (P<0.05). Conclusions CD5 may affect the chemotherapy sensitivity of Jeko-1 mantle cell lymphoma cell line through up-regulating its secretion of IL-10 via NF-κB signaling pathway.