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The goal of the Human Liver Cell Atlas (HLiCA) is to create a comprehensive map that defines the normal functions of diverse liver cell types and their spatial relationships over the human lifespan. This project fits within the goals of the Human Cell Atlas to create comprehensive reference maps of all human cells as a basis for both understanding human health and diagnosing, monitoring and treating disease. Through collection of samples from diverse individuals, data integration across technologies and overcoming liver-specific challenges for experimental methods, the HLiCA will map as many cell types and states as possible in healthy human livers from individuals across all ages and many ancestries. Establishing this HLiCA of healthy livers is a critical step to begin to understand perturbations in disease. The HLiCA will be available on an open-access platform to facilitate data sharing and dissemination. We expect that creation of the HLiCA will help to lay the foundation for new research initiatives to advance our understanding of liver disease, improve methods of tissue engineering, and identify novel prognostic biomarkers and therapies to improve patient outcomes. We describe key experimental and computational challenges to overcome in building the atlas and the potential impact of the atlas on disease research.