A new procedure to obtain single-polarization single-mode polymeric optical fibers is reported. The selective polarization confinement loss mechanism is obtained by applying external hydrostatic pressure in a specially designed side-hole microstructured polymer optical fiber. It is shown that, at λ = 588 nm, pressure around 380 bar allows inducing confinement loss as high as 35 dB/m for one polarization state while the other is guided with low loss (3 ×10-3 dB/m). The loss mechanism is shown to be related to coupling between the fundamental core modes and the cladding modes of the pressurized fiber. Finally, the possibility of tuning the single-polarization single-mode state with the input wavelength with fixed pressure or by introducing small changes in the inner ring of holes of the fiber cross section is presented.