Follow this official guide for
Yubikey setup with Windows 10 from Yubico
PS: I haven't tried this myself, proceed at your own risk
What you are trying to accomplish is to make Windows 10 require Yubikey when logging in.
It is helpful in preventing physical unauthorized access to your PC, because you need the Yubikey (hardware) to login to your PC - essentially a hardware 2FA.
-Use case for this is if your PC is in a public place like an office or in the living room of your house, or if it's in your room but you cannot or prefer not to lock your door with a key.
Note: It is important take note of your recovery code
I have a Yubikey myself, but I do not use it for Windows 10 login. I use it instead for websites and other services rather than encrypting with Windows 10.
-Always have 2 Yubikeys and associate them, so that if one breaks, you are not locked out of the website/service.
Bitlocker is a Windows 10 tool that can encrypt your entire drive for protection
Samsung encryption is the same, but is made by Samsung.
They are both software, unlike Yubikey which is hardware.
When you encrypt something, It cannot be accessed
UNLESS you open it. When it is in the opened state, and if there happens to be a trojan backdoor (Remote administration tool) that is connected to your PC and viewing what you're doing, then your data can be compromised. If however the attacker tries to steal your file but you encrypted it and did not open it, then he needs to break through that encryption which is challenging. That's where encryption comes in.
In the end, PC Security is still important. Avoid downloading and installing malicious programs, browser extensions, etc. Use a reliable anti-virus and anti-malware programs to thoroughly scan your PC to make sure there's nothing running in the background that's stealing your data. Be especially careful as well when installing browser extensions as some do some form of discrete data collection.
Encryption alone via Bitlocker, etc. isn't enough but it does make it a challenge for an attacker to try to crack that file if they do steal it from you.
Hardware 2FA like Yubikey also adds another layer of protection, but you must take note the recovery code or else you lose access to your PC.
If you're not using your PC and it is connected to the internet, I would recommend using a firewall to block all connection while you're away and then only re-enable it when you're using the PC.