Based on the advances of research in cognitive informatics and related fields, this paper attempts to develop a layered reference model of the brain that explains the functional mechanisms and cognitive processes of the natural intelligence. A variety of life functions and cognitive processes have been identified in cognitive informatics, cognitive science, neuropsychology, and neurophilosophy. In order to formally and rigorously describe a comprehensive and coherent set of mental processes and their relationships, an integrated reference model of the brain is established, which encompasses 37 cognitive processes at six layers known as the sensation, memory, perception, action, meta and higher cognitive layers from bottom up. The reference model of the brain may be applied to explain a wide range of physiological, psychological, and cognitive phenomena in cognitive informatics, particularly relationships between the inherited and the acquired life functions, as well as the subconscious and conscious cognitive processes.