Up to date, preparation of thermo‐responsive mixed‐matrix membranes (MMM) has only be described as small scale flat membranes or multi‐step processes for hollow fiber membranes. In this work, the development of thermo‐responsive MMM hollow fibers composed of polyethersulfone as membrane polymer and poly(N‐isopropylacrylamide) (PNIPAM) microgel particles via the wet spinning process is presented. PNIPAM particles are synthesized with (NP‐S, zavg 20°C = 105 nm) and without (NP‐L, zavg 20°C = 250 nm) sodium dodecyl sulfate and their thermo‐responsive behavior is characterized by dynamic light scattering. Particle size (NP‐S, NP‐L), particle content (10%, 15%) and the extrusion pressure in the wet spinning process (1.0–3.0 bar) are investigated as experimental parameters. Reversible thermo‐responsive behavior of the hollow fibers is demonstrated by water permeability measurements at different temperatures (20 and 50°C). The largest switching factors (R) are observed for the hollow fibers containing NP‐L. For 15% NP‐L and 1 bar extrusion pressure, water permeances between 0.5 and 6.0 L m−2 h−1 bar−1 are observed, corresponding to R = 12 and a dextran (500 kDa) rejection of 91% at 25°C.