Epitope imprinting has proved to be an effective way for fabricating artificial receptors for protein recognition. Surface imprinting over sacrificial supports is particularly favorable for generating high-quality epitope-imprinted cavities, but obtaining nanomaterials by this way is still a challenge. Herein, we propose a method for the synthesis of oriented surface epitope-imprinted open-mouthed polymer nanocapsules (OM-MIP NCs) by sacrificing asymmetric template-modified Janus nanocores. Amine/aldehyde functionalized SiO Janus nanoparticles were prepared via the molten-wax-in-water Pickering emulsion approach, an easy scale-up technique. Epitope templates and vinyl groups were coupled to the aldehyde-bearing major side, whereas polyethylene glycol (PEG) chains were grafted to the amine-modified side. Incomplete imprinted shells were then generated principally on the non-PEGylated side via aqueous precipitation polymerization, hence affording OM-MIP NCs after etching the SiO nanocores. 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 synthesized for sensing of BSA. Such NCs reached maximal fluorescent response within 15 min, greatly faster than the closed imprinted NCs within 130 min, proving good accessibility of their inner-surface imprinted cavities thanks to the open mouths. Furthermore, they showed excellent target protein detection performance, with an imprinting factor of 7.8, a limit of detection of 43.8 nM and a linear range of 0.2-6 μM. The recoveries in bovine serum samples at four spiking levels ranged from 99.2 to 107.2%, with relative standard deviations of 1.2-5.9%.