How to sed and replace string with a folder path

In circumstances where the replacement string or pattern string contain slashes, you can make use of the fact that GNU sed allows an alternative delimiter for the substitute command. Common choices for the delimiter are the pipe character | or the hash # - the best choice of delimiting character will often depend on the type of file being processed. In your case you can try

sed -i "s#_HOME_DIR_#$HOME_DIR#"

Also note that you mistyped your variable name $HOME_DIR (it does not start with an underscore).

$ HOME_DIR=/opt/my_home
$ echo "_HOME_DIR_/config/data/_DOMAIN_/users.conf" | sed "s#_HOME_DIR_#$HOME_DIR#"
/opt/my_home/config/data/_DOMAIN_/users.conf

Just fyi you may want to avoid using all-caps for user variables in your script - they should be reserved for system variables. Also the g switch is not necessary unless you want to make multiple replacements on a single line.