In this study, an Al2O3-40TiO2 coating was deposited on 20MnNiMo steel via atmospheric plasma spraying. The corrosion behavior of the coating was investigated in both artificial seawater and a simulated environment with hydrogen sulfide and high pressure. Additionally, ion dissolution experiments were conducted to evaluate the coating’s bio-friendliness. In artificial seawater, the corrosion rate (based on the corrosion current) of the Al2O3-40TiO2 coating initially decreased before increasing. It was speculated that the blocking of corrosion products in the defect channels was helpful in delaying the progress of corrosion in the early stage. The coating had a corrosion current on the order of 10−6 A/cm2 in artificial seawater, suggesting good protection in conventional seawater environments. In the simulated environment, the corrosion rate (based on the weight loss) of the Al2O3-40TiO2 coating showed a continuously declining trend. It was deduced that, unlike corrosion products in artificial seawater, the corrosion products in the simulated environment (e.g., metal sulfide) might be more chemically stable, leading to a longer blocking effect. Therefore, a minimal corrosion rate of 0.0030 mm/a was obtained after the coating was immersed for 30 days. The amount of dissolved coated elements was negligible and there were only small amounts of dissolved non-coated elements such as Ni and Mo. The developed coating can be considered to be highly biofriendly if the non-coated area of the specimen is well sealed.