The west African country has been buffeted by falling prices for both oil and uranium, two of its main exports, as it struggles against jihadist attacks.
Protesters flooded the streets of Niamey chanting anti- regime slogans before holding a meeting in front of parliament, where they shouted "Life is too hard" and "Leave, that's enough".
The march was called by an alliance of 11 opposition groups.
"This mobilisation is additional proof that we have had enough," said Soumana Sanda, a former health minister who is now an MP for the Nigerien Democratic Movement (MODEN).
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MODEN is the party of Hama Amadou, who lost a run-off election against Issoufou last March.
That vote that was boycotted by the opposition after Amadou was jailed on charges of baby trafficking, which he claims are politically motivated.
The demonstrators also called for the release of "political prisoners", referring to several senior government figures arrested by the regime, some in connection with a failed coup in December 2015, others accused of embezzling public funds.
They also condemned the French, German and US military bases in the country, calling them a "liquidation of the country's sovereignty".
UN Security Council envoys are currently on a mission to the Lake Chad region, including a visit to Niamey, to focus global attention on the humanitarian emergency triggered by the Boko Haram insurgency.
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