Epitope imprinting is an effective way to create artificial receptors for protein recognition. Surface imprinting with immobilized templates and sacrificial supports can generate high-quality imprinted cavities of homogeneous orientation and good accessibility, but it is still challenging to fabricate nanoscale imprinted materials by this approach. Herein, we propose a method for the controlled synthesis of open-mouthed epitope-imprinted polymer nanocapsules (OM-MIP NCs) by limiting the imprinting polymerization on the template-bearing side of the Janus nanoparticles (JNPs). Concurrent bromoacetyl (Ac-Br) and 2-bromoisobutyryl (iB-Br) functionalization of the major portion of SiO2 nanoparticles is achieved via the molten-wax-in-water Pickering emulsion approach. The cysteinyl-derived epitope templates are immobilized through the Ac-Br groups, and then surface imprinting is fulfilled via ATRP initiated by the iB-Br groups. The SiO2 supports are partially etched and then PEGlated, affording OM-MIP NCs with a PEGylated nanocore. The inside nanocore can facilitate collection of the NCs by centrifugation, and its PEGylation can inhibit non-specific binding. The surface imprinting can be optimized through the ATRP time, and the etching can be tailored via the concentration of NH4HF2 employed. For proof-of-concept, with a C-terminus nonapeptide of bovine serum albumin (BSA) chosen as a model epitope and polymerizable carbon dots added to the pre-polymerization solution, fluorescent OM-MIP NCs were fabricated for BSA sensing. The as-synthesized NCs exhibited satisfactory detection performance, with an imprinting factor of 6.1, a limit of detection of 38.1 nM, a linear range of 0.25-6 mu M, and recoveries of 98.0 to 104.0% in bovine serum samples.