That is God’s most severe punishment. A rift between God and Cain. Evil is removed from the circle of those who follow God. That does not just happen. He who hardens himself in sin, like Cain, will have to deal with (God’s) discipline (see the laws of Moses in Deuteronomy 13:5; Deuteronomy 17:7; Deuteronomy 19:19, etc.; for the New Testament, see 1 Corinthians 5:13).
Cain is sent away, left to himself. No heavenly father. Complete loneliness, harbinger of hell in all its hideous reality. Think of Christ who was forsaken by the Father (Matthew 27:46). After paradise and the sin of Adam and Eve, God did not go that far. There was no curse on man given then. But Cain rejects God: in a premeditated murder, by not responding to God’s call (Genesis 4:7), by rejecting God’s repeated call (Genesis 4:9). Cursing is the opposite of blessing: fraught with mischief.
11 And now you are cursed from the ground, which has opened its mouth to receive your brother’s blood from your hand.