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As a typical antibiotic pollutant, tetracycline (TC) is producing increasing threats to the ecosystem and human health, and exploring convenient means for monitoring of TC is needed. Here, we proposed alkali-etched imprinted Mn-based Prussian blue analogues featuring superior oxidase-mimetic activity and precise recognition for the colorimetric sensing of TC. Simply etching Mn-based Prussian blue analogues (Mn-PBAs) with NaOH could expose the sites and surfaces to significantly improve their catalytic activity. Density functional theory calculations were employed to screen the molecularly imprinted polymer (MIP) layer for target identification. Consequently, the designed Mn-PBANaOH@MIP possessed the rich channels for substrates to get in touch with the active Mn-PBANaOH core, showing an excellent catalytic capacity to trigger the chromogenic oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB) without the use of H2O2. If TC was introduced, it would be recognized selectively by the MIP shell and masked the channels for TMB access, resulting in the obstruction of the chromogenic reaction. According to this mechanism, selective optical detection of TC was achieved, and performance stability, reusability, and reliability as well as practicability were also verified, promising potential for TC monitoring in complex matrices. Our work not only presents an effective way to enhance the enzyme-like activity of Prussian blue analogues but also provides a facile approach for TC sensing. Additionally, the work will inspire the exploration of molecularly imprinted nanozymes for various applications.