Recently, a new carbon allotrope-biphenylene (BPN), has been successfully fabricated. The first-principles calculations were utilized in this work to investigate the mechanical property of BPN with substitutional doping, considered to adjust the anisotropy of mechanical properties. The mechanical anisotropy of BPN is enhanced by 1.7 % and 10.8 % after double doping with B and N atoms, respectively, without changing its thermodynamic stability. Our findings demonstrate that atomic doping can tune the anisotropy of the mechanical property of the BPN monolayer. By choosing a right orientation of BPN for optimal mechanical properties, our study provides great promise for design of sensing and flexible electron devices.