Hemispheric asymmetry is an important feature of the human brain that develops before birth. The inherent asymmetry of the brain is of great significance for cognition, language and other functions in humans. An understanding of normal brain and asymmetry development in the earliest period will further our understanding of how the different hemispheres prioritize specific functions. However, the core genetic mechanism is still unknown. Here, we analysed the developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. The patterns of protein expression changes in the bilateral frontal lobes were different. Our results show that brain asymmetry can be observed in the early stage of foetal development. Human brain asymmetry is the result of differential gene expression before birth in the early foetal stage and develops before functional asymmetry. Researchers can use these findings to further investigate the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics research and human brain mapping studies.