This study discusses the issue about portrayal of desperation reflected in Jojo Moyes’ Me Before You novel (2012) which is analyzed by using Existentialism study. The objectives of this study are to describe the characteristic of desperation through Existentialism, to identify the indicators of desperation, and to reveal why desperation can be the basic issue of Me Before You novel. This study is descriptive qualitative research. The primary data source is Me Before You novel (2012) by Jojo Moyes, while the secondary data source are taken from books, websites, articles, dictionaries, and others that match with this study. The result of this study as follows: Firstly, the characteristics of desperation can be found through five principle of Existentialism theory; Secondly, there are five indicators of desperation which are losing interest in daily activities, being self-defeating, becoming more emotional, losing self-identity, and lacking productivity; and the last, desperation can be the inspiration of the novel based on Jojo Moyes’ family members real life and a story that she heard from radio