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People with autism deserve specific attention as concern environmental comfort, well-being and accessibility of environments, not only because they are a significant and growing share of the total population, but also because they can show special sensitiveness to the variation and value of several environmental parameters. In this work, the main building-related critical issues connected to the special environmental sensitivity in the autism spectrum condition are highlighted and analysed. By means of a questionnaires’ survey among parents and caregivers of people with autism, their sensitivity to different thermal, visual, acoustic and indoor air quality stimuli was evaluated. Then, a list of risk factors was prepared for a residential context, classifying them into environmental risks, leading to discomfort and dangerous response for people with autism; and accidental risks, deriving from unpredictable events, even more dangerous for people with special perceptual disorders. According to the outcomes of the survey and based on literature considerations, probability and severity of environmental and accidental risks were estimated on a scale from 1 to 5 in the different rooms of residential buildings. This permitted to draw up a hypothetical system of possible interventions and solutions to be considered during the design phase, establishing a different priority in the different rooms of a dwelling, in order to increase the occupant’s comfort, safety and autonomy, and improving physical and psychological well-being.