Objective To explore the relationship between protein levels of SAMHD1 expression with viral load of SIV in the SIVmac239-infected CEMx174 cells.Methods CEMx174 cells were infected with SIVmac239, and the cells and supernatant were collected daily for analysis. The viral loads and the SAMHD1 mRNA level were detected by real-time RT-PCR and the level of P27 and SAMHD1 proteins were detected by Western blotting. Results The mRNA level of intracellular SAMHD1 gene was increased and SAMHD1 protein decreased gradually when CEMx174 cells were infected with SIVmac239. Conclusions There is a positive correlation between viral load in the supernatant and the mRNA level of SAMHD1, and a negative correlation between the increase of P27 protein and the decrease of SAMHD1 protein in the SIVmac239-infected CEMx174 cells.