What version of Excel?
In general, you cannot change the column letters. They are part of the Excel system.
You can use a row in the sheet to enter headers for a table that you are using. The table headers can be descriptive column names.
In Excel 2007 and later, you can convert a range of data into an Excel Table (Insert Ribbon > Table). An Excel Table can use structured table references instead of cell addresses, so the labels in the first row of the table now serve as a name reference for the data in the column.
If you have an Excel Table in your sheet (Excel 2007 and later) and scroll down, the column letters will be replaced with the column headers for the table column.
If this does not answer your question, please consider editing your question to include the detail you want to learn about.