Real Madrid will look to avoid becoming the latest Primera Division big gun to fall foul of Hercules this weekend while Barcelona host Sevilla.
In their last three league games Madrid have also netted 16 goals, and they boast the leading attack (22 goals scored) and best defence (four goals conceded) in the division.
It is an enviable position to be in, but they will be well aware of the threat promoted Hercules could pose to their unbeaten record this weekend.
The Alicante side have had a mixed time since returning the top flight and are currently in 13th spot with nine points, but they have proven themselves to be no pushovers - especially against the top teams.
Esteban Vigo's men have already recorded 2-0 wins over Barcelona and Sevilla, while they also ended Villarreal's five-match winning streak with a 2-2 draw last week.
Of the leading clubs, only local rivals Valencia have managed to claim a three-point haul against the newcomers, sneaking a 2-1 win in round three after netting twice early on.
Madrid defender Marcelo said: "We must be careful because Hercules are growing with every game. They are going to make things difficult for us."
Hercules striker Nelson Haedo Valdez, who scored both goals in the win over Barca at the Nou Camp, said on Paraguayan radio: "If we were capable of beating Barca, why can't we do the same against Madrid? We respect them, but don't fear them."
Should Madrid, who next week go to AC Milan in the Champions League before hosting bitter rivals Atletico at the Bernabeu, slip up then they could be replaced at the summit by either Villarreal or Barca, who are both just one point behind.
Villarreal missed the chance to go top when they were held by Hercules, but they will hope for better when they go to Sporting Gijon this weekend.
Barcelona have a tricky-looking encounter against Copa del Rey holders Sevilla, who are five points adrift of Pep Guardiola's men but look a side on the up under new coach Gregorio Manzano.
Since replacing Antonio Alvarez, Manzano has guided the Andalusian side to five wins in six matches in all competitions, the latest being a 4-0 thumping of Real Union in the first leg of their Copa del Rey last-32 tie on Wednesday night.
Striker Alejandro Alfaro struck his side's third goal against Union and he hopes they can have another good night against Barca.
"We have a good squad, good players and a good coach, and we can make things very difficult for Barcelona. I hope that's the way it will be," he said.
Fourth-placed Valencia will attempt to get back on track when they host bottom club Real Zaragoza, who are still searching for their first win in La Liga this season.
Valencia had enjoyed a flying start to the campaign but back-to-back league defeats to Barca and Real Mallorca have left Unai Emery's men four points behind leaders Madrid.
Aside from Zaragoza, the only other side yet to win in the league are second-bottom Deportivo La Coruna.
Miguel Angel Lotina's side, who have also only scored once from open play this season, are at home to Espanyol.
In this weekend's other games, Atletico Madrid hostAlmeria, Getafe go to Athletic Bilbao, Malaga go in search of their first home points against Real Sociedad and Racing Santander take on Osasuna.
On Monday evening, Real Mallorca are at home to Levante.
