Hydrogen sulfide (H2S) is toxic and corrosive at high concentrations and pressures. Adsorption methods are suitable due to their low energy consumption, low cost, and high efficiency. Synthesis and optimization of structural and operational parameters of specific molecularly imprinted polymers (MIPs) Nano adsorbents for H2S gas adsorption carried out using response surface design methodology. The optimal polymerization conditions of MIPs included 16 experiments. The amounts of template molecules (1–5 mmol), cross-linker (5–20 mmol), functional monomer (2–12mmol), porogen solution (acetonitrile/ethyl acetate v/v 1–9%), elution solution (acetic acid/methanol 20/80) and initiator (25–100 mg) were optimized using Taguchi method of experimental design. We used the SRK equation of state for the molar mass of the gas on a fixed bed with a height of 400 mm and an inner diameter of 10 mm. Finally, physical properties were determined using FTIR, XRD, FE-SEM, and BET. Statistical analysis showed that the signal-to-noise ratio between the template molecule, cross-linker, and functional monomer was 2:15:2.5, and the optimal adsorption value occurred at a volume ratio of acetonitrile/ethyl acetate of 1:9 and initiator of 75. In this study, the surface is MIPs@H2S. Variance analysis showed that all Nano-adsorbents followed a second-order model, temperature and adsorbent dosage were the most critical variables in the process, and the equilibrium adsorption of all Nano-adsorbents followed the Langmuir isotherm and second-order synthesis model. The regeneration study highlighted that the Nano-adsorbent is a promising adsorbent with high reversibility and stability for H2S gas. Finally, the selectivity results of specific adsorption of H2S gas by CO2/H2S/CH4 gas mixture of MIPs@H2S were significantly higher than that of Non-imprinted polymers (NIPs) Nano adsorbent.