Macadamia is a native Australian nut crop belonging to the diverse Gondwanan family Proteaceae. Genetic resources are extremely limited, restricting macadamia breeding programs and comparative genomic studies. In this study, over 95 gigabases of sequence data from the genome and transcriptome of Macadamia integrifolia cultivar HAES 741 were assembled. In total, 35,337 protein-coding genes were predicted and of these, 90% were supported by RNA-seq based expression evidence. Macadamia represents an ancient rainforest-restricted Proteaceae lineage and comparative gene family analysis provides evidence for an expansion of gene families involved in pathogen recognition, plant defense and monoterpene synthesis. Although rare among plant species, many domesticated food plants are cyanogenic. The relatively high proportion of cyanogenic species in the Proteaceae indicates that cyanogenesis is an important defense strategy in this family. Several of the candidate genes for cyanogenic glycoside biosynthesis that were identified were highly expressed in the M. integrifolia leaf, shoot and flower tissues examined. These first genomic resources for the Proteaceae and for macadamia provide a platform for comparative genomics, and new opportunities to identify the genes and markers associated with traits of importance for conservation, domestication and plant breeding.