Hernández began his career with Central Español and Peñarol, and spent five and a half seasons in Italy with Palermo before joining Hull City for a club record £10 million in September 2014.

Nicknamed La Joya,[2] he started his professional career with Uruguayan side Central Español, immediately scoring five goals in his first four games.

On 2 February 2009, Italian Serie A club Palermo completed the signing of Hernández, where he joined fellow Uruguayan Edinson Cavani.

[9] The following campaign, he struck 14 times in 28 Serie B games as the Sicilians returned to the top flight, netting braces in away victories over Padova and Siena, both of which included a penalty kick.

[13] In his next home game against Manchester City on the 27th, he won a penalty after being fouled in the area by Eliaquim Mangala, and scored it in an eventual 2–4 defeat.

[17] On 16 January 2016, in a Championship match against Charlton Athletic, Hernández scored his first club career hat-trick in a game that finished 6–0, taking his league tally to 14 goals for the season.

[20] In January 2017, Hernández missed two penalties in the space of two minutes in a FA Cup fourth round match verses Fulham.

[31] Hernández was linked with Nottingham Forest after his release from the Russian capital, but instead signed for Al Ahli SC of the Qatar Stars League, believing that the move would help him back into the national team.

[34] He was part of the Uruguayan team which won the 2011 Copa América in Argentina, making substitute appearances in their opening match and their semi-final victory, both against Peru.

He was chosen by Óscar Tabárez for the London 2012 Olympic Uruguay squad, making a half-time substitute appearance in the 0–2 defeat to Senegal at Wembley Stadium, in an eventual group stage exit.

[36] Hernández was also included in the Uruguayan squad for the 2014 FIFA World Cup, making substitute appearances in their opener against Costa Rica and round of 16 match against Colombia, both defeats.