Animal bones are a high-quality source of protein and comprehensive nutrients and improper handling can cause resource wasting and environmental issues. Pretreatment before enzymatic hydrolysis of bone could significantly improve the enzymolytic efficiency, which is an essential step to achieve high value-added utilization of bones. This study investigated the effect of lipase pretreatment on the enzymatic hydrolysis of bones. The degree of hydrolysis after lipase pretreatment was 12.58%, which was 8.19% higher than that without pretreatment. Lipase pretreatment was optimal at 9% substrate concentration and initial pH 7.5, with 0.08% lipase, followed by 4 h incubation at 40 °C. Mechanism analysis indicated that lipase pretreatment improved the enzymolytic efficiency by significantly decreasing the lipid content, and changing the surface structure and surface element content of C, N, and O, promoting the attachment of alkaline protease onto the sample. Overall, lipase pretreatment was an effective method to reduce the costs of production.