Abstract: In the context of the digital economy, the Internet has given new impetus to the development of enterprises, but the resulting data security problems have brought great challenges to interrelated supply chain enterprises. This paper uses the game theory method to explore the decision-making of supply chain data security investment considering the substitution of information assets, which is composed of single supplier and two information asset substitution retailers. The study finds that, when the market scale is small, the supplier's data security investment is positively correlated with the information asset substitution rate, while the retailer's data security investment is negatively correlated with the information asset substitution rate. When the market size is large, the supplier's data security investment is negatively correlated with the information asset substitution rate, while the retailer's data security investment is positively correlated with the information asset substitution rate. Supplier's data security investment is positively correlated with investment effectiveness. Retailer's data security investment is negatively correlated with investment effectiveness when the market size is small, and positively correlated with investment effectiveness when the market size is large. The profits of suppliers and retailers decrease with the increase of information asset substitution rate, and the profits of suppliers and retailers increase with the increase of investment efficiency. The conclusions of this paper can provide reference for the decision-making of data security investment in supply chain enterprises.