What is the subject of speech when he holds skull Yorick?

The subject of Hamlet's speech while holding Yorick's skull is the inevitability of death and the ephemeral nature of life.

Hamlet reflects on how the once vibrant and funny jester Yorick is now nothing more than a hollow skull. He contemplates the decay of the body and the fading of memories, questioning the meaning and purpose of life.

This iconic scene in Act 5, Scene 1 of Hamlet is a powerful reminder of the fleeting nature of existence and the ultimate fate that awaits all of us.