Se(IV)- and Te(IV)-containing wastewater usually contains salt, which reduces the activity of conventional microorganisms and may affect their microbial treatment. So far, salt-tolerant Se(IV)- and Te(IV)-reducing bacteria are very limited. Moreover, the detailed molecular response of microbial reduction of Se(IV)/Te(IV) under saline conditions has yet to be reported. In this study, the Se(IV) and Te(IV) reductive processes and mechanisms were investigated with the employment of a marine bacterium Shewanella sp. CNZ-1 (CNZ-1) using process and kinetic analyses, enzymology and RT-qPCR analyses, and differential proteomics approaches. Our results showed that CNZ-1 can effectively reduce Se(IV) and Te(IV) to Se0 and Te0 with the max k (R2) values of 0.0412 h−1 (0.86) and 0.0292 h−1 (0.91) under 2% NaCl conditions, respectively. The mechanism study showed that CNZ-1 mediated Se(IV) reduction was an enzyme-based reductive reaction, whereas CNZ-1 mediated Te(IV) reduction was more like a resistance-related detoxification process (including both bioadsorption and bioreduction). The bioreduction of Se(IV) was mainly depended on functional membrane proteins (>4-fold; e.g., nitrite reductase, polysulfide reductase and fumarate reductase), while proteins related to efflux system and stress resistance system (>2-fold; e.g., Type II secretory pathway and phage shock proteins) were essential for the Te(IV) bioreduction process. Overall, our findings expanded the understanding the fate of Se(IV) and Te(IV) in the saline environment and provided guidance for Se(IV) or Te(IV) pollution control.