Previous research showed that co-down-regulation of caspase-3/7 in rCHO cells, unlike Bcl-2 overexpression, did not effectively block apoptotic cell death induced by 3mM sodium butyrate (NaBu). Here, it is found that the control of autophagy is also related to this different response to NaBu treatment. With NaBu treatment, co-down-regulation of caspase-3/7 enhanced autophagy induction, whereas Bcl-2 overexpression delayed onset of autophagy induction in a Beclin-1 independent manner. The blockage of autophagy showed a detrimental effect on cell viability even in the Bcl-2 overexpressing cells, which suggests the importance of autophagy control for successful anti-cell death engineering of rCHO cells.