Kakuzu stands with the advantage here because her fighting style leaves her completely vulnerable to his preffered style. I shall begin by listing exactly what strengths Tsunade has and how Kakuzu counters them.
1) Strength
2) Byakugou
3)Katsuyu
Kakuzu vs Tsunade's Strength
Doton-Domu is more commanly known as Earth Style: Earth Spear (AKA: Iron Skin technique). This ability gives Kakuzu skin as hard as diamond meaning that other than a Lightning style attack, nothing can penetrate his defense. As a result, Tsunade's chakra enhanced punches would do nothing to counteract his skin, and as such are ineffective. Considering this technique also survived a Spiked Human Boulder, Mattatabi's paw strikes (and possibly her flame breath), and even explosive tags, it is safe to say that this technique is capable of nullifying her strength.
Byakugou
The Byakugou is the largest factor in making this fight Difficult. This is simply because she can heal herself instantly causing an extended fight. However, as both a Kage and a Senju, this reputation will give Kakuzu insight into her likely having this technique (he did fight Hashirama afterall). So without this comming as a shock, Kakuzu can be prepared for it.
For starters, his AoE Masks are capable of forcing her Jutsu into healing her meaning that she will begin to wear down/ use up its power. After that, His natural skills in Taijutsu and Doton: Domu keep her healing advantage from gaining an upperhand as far as landing a fatal blow. Also, Kakuzu can use his tendrils to cause physical damage forcing even more use of the Byakugou. Even if Tsunade pulss the strings to bring him into close range...his Doton: Domu would protect this attack from being fatal.
As such, Kakuzu merely has to outlast her, and considering he fought Kakashi, Ino, Chouji, Yamato, Shikimaru, and Naruto without showing signs of tiredness, I would say he has the endurance to face her. Also, he managed to have enough Stamina to escape her Grandfather Hashirama even after attacking him.
Katsuyu
Katsuyu for the most part would add a chakra reserve for Tsunade. Because of the immense size, the creature is an easy target. If Katsuyu deployed her Acid, Kakuzu's wind mask can simply alter the direction of the acidic substence by changing the course of the wind using Fuuton: Asugai (Air Pressure Damage). This leaves Katsuyu to either get hit by attacks, or to disperst into the small Katsuyu pieces. As small pieces, they practically lose their combat efficiency, and are now subjected to being being Healing bounuses/chakra reserves.
Key Counter Argument
Some would counter by saying that Tsunade possesses a Lightning Affinity; however, this is only presumed, and has not been confirmed. In addition, in her fight with Madara (where she would display all of her might), she did not use any Raiton techniques. As I recall, the only lightning oriented technique she used was when she altered Kabuto's body network. Considering Kakuzu's own intelligence and experience, I cannot see this jutsu being any more troublesome for him than it was for Kabuto. Not to mention his masks could simlpy protect him by moving them until he figured it out.
Conclusion
In conclusion, this match becomes a bit of an endurance match; however, Kakuzu's attack style is overly advantageous compared to Tsunade's because he is a Mid-Long range specialist that is also extremely talented in Taijutsu (capable of outmatching a notable Taijutsu fighter that held the Sharingan: Kakashi). As such, through his masks, he can force Tsunade's reserves down with little effort from his own reserve. For close encounters, Doton- Domu protects him from Tsunade's One-Shots as well as enhances his own physical strength to a level capable of breaking steal doors in a half effort punch.
Tsunade is far from weak, however, in this match up Kakuzu's particular fighting style and abilities are a bad match for Tsunade's personal fighting style.