Self-immolation is a self-destructive conduct described since antiquity. Its frequency is variable from one country to another and it is a real public health problem in parts of the world. In Tunisia, after the 2011 revolution the problem of self-immolation protest has been highly publicized giving the impression of an increase in this phenomenon. This is a retrospective analysis of all fatal self-immolation cases, collected over a 20-year period (1996–2015) at the Forensic Medicine Department of the Farhat Hached University Hospital, Sousse, Tunisia. A total of 41 cases were collected, of which 23 were men (56%). The mean age was 36.1 years. Prior to 2011, 78.9% of the victims of self-immolation were women and after 2011, 86.4% were men. The rural origin of the victims was found in 56.25% of the cases. History of psychiatric illness was found in four individuals. The self-immolation took place in the victims’ homes in 19 cases (46.3%). It came after a conjugal or family conflict in 14 cases (34.1%) and it is of protest character in 8 cases (19.5%). This study confirmed the increasing frequency of self-immolation in Tunisia after the 2011 revolution and noted a change in the victims’ profiles.