Maybe; if you bought it for almost nothing and it's value has increased a lot.
If married, then you can exclude $500,000 of gains for the sale of home.
Gain = sale proceeds - [minus] your initial purchase price + improvements.
Example:
In 1990, you & your spouse paid $100,000 for your house,
then in 2022, you both sold your house for $400,000.
Gain = $300,000 (so, no income tax in this example because gain < $500k).
Alternatively:
In 1990, you & your spouse paid $100,000 for your house,
then in 2022, you both sold your house for $700,000.
Gain = $600,000 and taxable gain = $100,000
(gain - [minus] $500,000 exclusion mentioned above).
(For these examples, sale proceeds are not reduced by a mortgage payoff but they are reduced by realtor fees, attorney fees, conveyance taxes, and any credits given to the buyer from the seller.)
Either spouse can own the house when it's sold but both spouses must have lived in the home as their main home for 2 of the last 5 years.
If you're NOT married, then you can only exclude $250,000 of gains.