In order to analyze the temperature drift simulation and compensation method of evanescent wave organic matter sensor. This paper introduces the optical fiber evanescent wave biosensor system, analyzes the social and economic benefits of the optical fiber evanescent wave biosensor system, and verifies the feasibility of the system with the help of simulation method. Aiming at the zero drift, taking advantage of the fast speed of MPU, a standard signal source is added. Before sampling the input data, the standard signal is sampled to measure its drift, and the amount of drift is added to the calculation formula of signal quantity, so that its drift can be corrected automatically. Then take the zero temperature compensation of electronic scale as an example, set the sampling value of the measured object as X, the maximum allowable zero tracking drift as ±E (E > 0), the resolution of the measurement system as ±ε (ε > 0), and the zero value at no-load is d zero, which is stored in the temporary zero unit of the single chip microcomputer system. The experimental results show that the correct voltage value at a certain temperature can be calculated through the cyclic program of C language. This method has higher accuracy than two-dimensional regression method, less calculation than neural network method, faster calculation speed, less storage space, and is more suitable for the requirements of low-cost single chip microcomputer. Therefore, this can reduce the cost. Although the accuracy is not as high as that of neural network, the error of 0.8 % can meet the actual needs, and has been put into practical application. At the same time, by summarizing the experiment of compensation method in the simulation system, the in-depth analysis of temperature drift simulation and compensation method of evanescent wave organic matter sensor is realized.