RNA interference (RNAi) technology has become a novel tool for silencing gene expression in cells or organisms, and has also been used to develop new therapeutics for certain diseases. This review describes its other application of using RNAi technology to increase cellular productivity and the quality of recombinant proteins that are produced in Chinese hamster ovary (CHO) cells, the most important mammalian cell line used in producing licensed biopharmaceuticals in these days. The approaches reported include the silencing of apoptosis-associated gene expression, protein glycosylation-associated gene expression, lactate dehydrogenase involved in cellular metabolism, and dihydrofolate reductase used for gene amplification. All of these works belong to the single component approach therefore depends strongly on the identification of the down-regulation of the critical target gene which can markedly influence the cellular functions associated with recombinant protein expression in CHO cells. Future RNAi approaches can be extended to silence multiple targets involved in different cellular pathways for changing the global gene regulation in cells, as well as the targets related to microRNA molecules for cellular self regulation.