Transition metal selenides (TMSs) with high specific capacities are regarded as promising electrode materials for capacitive deionization (CDI), but are hindered by insufficient electronic conductivity and large volume effects. Herein, we propose an interfacial-confined in-situ derivation strategy for constructing fluoride-free Ti3C2Tx MXene supported NiSe2/CoSe2 nanoparticles hybrids (Ti3C2Tx@NiSe2/CoSe2), through utilizing the redox reaction products derived from the molten salt etching process as precursors. The robust Ti-O-Ni/Co chemical bonding between Ti3C2Tx and NiSe2/CoSe2 ensure the ultrasmall nanosized NiSe2/CoSe2 particles evenly distributed that leads to expose abundant multi-interface active sites and provides additional pseudocapacitance. Significantly, the fluoride-free Ti3C2Tx MXene with superior electrical conductivity, adjustable surface functional groups and multi-channel pathway further promotes the electrochemical reaction kinetics and preserves significant structural integrity of NiSe2/CoSe2 nanoparticles via the space confinement effect. Ti3C2Tx@NiSe2/CoSe2 exhibits exceptional brackish water desalination performance (130.0 mg g−1 at 1.6 V) and superior cycling stability in the hybrid CDI system. The four-cell CDI stack effectively reduces ion levels in brackish and lake waters to meet Chinese drinking water standards (GB 5749–2022), offering a techno-economic benefit with a treatment cost of $ 0.39 m−3. The proposed strategy in this work enables the rational use of Lewis acidic etching by-products and paves the way for the preparation of MXene/TMSs compound hybrids as advanced CDI anodes.