Biofouling significantly impacts marine environments and economies through pollution and economic loss. Artificial nanozymes, resembling haloperoxidase, are highly effective in combating biofouling due to their ability to facilitate the conversion of Br− to HBrO, thereby inhibiting the survival and proliferation of microorganisms. However, this process necessitates the presence of H2O2. To achieve haloperoxidase mimicry in biofouling prevention without external H2O2, a bifunctional polyoxometalate (POM) with abundant oxygen vacancies has been developed. This compound simultaneously exhibits haloperoxidase mimicry and photocatalytic H2O2 generation. Theoretical analyses suggest that oxygen vacancies elevate the d-band center, improving the adsorption of H2O2 and Br-, and thus enhancing haloperoxidase mimicry. The POM compound demonstrates notable H2O2 production capabilities, with a rate of 1.77 mmol·h−1·g−1, attributed to oxygen vacancies facilitating electron-hole pair separation. This advancement allows for haloperoxidase mimic biofouling prevention without the need for added H2O2. This study not only elucidates the structure–activity relationship in haloperoxidase mimicry and photocatalytic H2O2 production but also presents an effective and eco-friendly method for biofouling prevention.