Objective: To research build a kind of occupational disease risk assessment model which provides scientific basis for prevention and control of occupational diseases. Methods: Based on the principle of information diffusion, this paper uses spread function to extend the incomplete gathered information, establishes the mapping relationship between observation samples and risk probability distributions, and constructs the occupational disease risk assessment model, to analyzes the risk data of occupational disease reported cases in Guangdong Province in the past five years. Results: Through evaluation analysis, every year, 200-300 cases of pneumoconiosis probability is 67.77%, 100-200 cases of occupational poisoning probability is 68.52%, 20-40 cases of occupational cancers probability is 71.62%, each year, the incidence of occupation otorhinolaryngology and oral diseases in 200 cases was 62.23%. Conclusion A model of occupational disease risk assessment based on information diffusion theory is constructed, the evaluation result is basically consistent with the actual situation of occupational disease, which can provide reference for occupational disease prevention and control.