The safety monitoring and condition assessment system (SMCAS) constructed for the Nanjing Yangtze River Bridge (NYRB) and its functions are introduced in this paper. The SMCAS, which allows the bridge to be monitored and evaluated under normal operating conditions, is composed of sensor system, signal sampling and processing system, and structural monitoring and condition assessment system. The objective is to evaluate objectively and accurately the integrity and safety of the bridge and operating conditions in real time for the NYRB. According to requirements of safety monitoring for the NYRB, representational and dominative monitoring items and layout of measuring points are determined by combining theoretical analysis with measured data analysis. Key techniques to build and realize the SMCAS for the NYRB, such as automation of safety monitoring, reliability, special software designing, massive monitoring data analysis and processing, data communication etc., are also discussed. The SMCAS for the NYRB can be used for reference for a similar monitoring system.