Co-adsorption with molecules that strongly adsorb on metallic surfaces is beneficial in improving the surface-enhanced Raman spectroscopy (SERS) detection sensitivity of some weakly adsorbed molecules or ions. In this paper, the co-adsorption of four deoxyribonucleic acid (DNA) bases: adenine, guanine, cytosine, and thymine with ClO-4 was studied. Factors like adsorption ability, applied potentials, and coexisting anions were examined to illustrate how they affect co-adsorption. We found that the four DNA bases in their protonated forms could co-adsorb with ClO-4. Among them, thymine with the weakest adsorption ability on Au showed the weakest co-adsorption ability with ClO-4. In addition, repulsion from both negative potentials and reduced SERS enhancements of Au substrates at relatively positive potentials led to a decrease in the SERS intensity of ClO-4. Moreover, anions such as Cl-, NO-3 , and SO2-4 were shown to influence the co-adsorption of ClO-4 with adenine based on a dynamic and reversible competitive co-adsorption process. The above results are very helpful in optimizing the SERS detection sensitivity of weakly adsorbed ions or molecules via the co-adsorption method.