Non-alcoholic fatty liver disease represents the most common chronic liver disease in obese children of industrialized countries. Nowadays the first line of treatment of pediatric non-alcoholic fatty liver disease is based on dietary and lifestyle intervention; however compliance to these interventions is very difficult to maintain in long term period. This editorial discusses about docosahexaenoic acid treatment as possible novel approach for non-alcoholic fatty liver disease in obese children. Docosahexaenoic acid may modulate the inflammatory response, improve insulin sensitivity and could be effective in enhancing intestinal barrier integrity, essential to protect a healthy gut-liver axis. Indeed alteration of gut microbiota composition and increased intestinal permeability may rise the exposure of liver to gut-derived bacterial products, causing activation of signalling pathways implicated in liver inflammation and fibrogenesis. This mechanism has been observed in vitro and animal models of non-alcoholic fatty liver disease but also in a clinical study in adults. While evidence suggests that n-3 long-chain polyunsaturated fatty acids supplementation may decrease liver fat in adults, in pediatric population only a study examined this topic. In obese children with non-alcoholic fatty liver disease well designed randomized controlled trials are needed to better clarify the possible efficacy of docosahexaenoic acid treatment, and underlying mechanisms, to identify the optimal required dose and to evaluate if the docosahexaenoic acid effect is limited to the duration of the treatment or it may continue after the end of treatment.