The Portuguese forward steered home Andrew Robertson's cutback to open the scoring after 97 seconds, before another simple finish following fine work from Mohamed Salah put Liverpool two goals up and in command inside 32 minutes.
Midfielder Thiago Alcantara added to his stunning goal against Porto in the Champions League in midweek with a third five minutes later and Virgil van Dijk helped himself to a fourth against his former club early in the second half. Jota had a great chance to complete his hat-trick but could not connect from close range as Liverpool eased to a win that lifted them above champions Manchester City, who play West Ham United on Sunday, and one point behind leaders Chelsea.
Southampton had their moments but they could not cope defensively and the loss left them 14th in the standings.
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