This paper examines the factors affecting human resource for small and medium-sized enterprises (SMEs) in the Fourth Industrial Revolution in Vietnam by using survey data from labors who worked in SMEs in Thai Nguyen, Vietnam. It then empirically examines the relationship between human resource development and a range of factors, using Exploratory Factor analysis and Multivariate regression analysis. The results indicate that six factors were more strongly affected SMEs human resource development in Industry 4.0 such as SMEs human resource development policy, System of training and vocational institutions, The development of science and technology, State and provincial policies for human resource development for SMEs, Business manager and Individual employee. In Vietnam, State and provincial policies for SMEs human resource development is the most influential factor on human resource development in Industry 4.0.